Thyroid dysfunction in patients with Down syndrome: Results from a multi ‐institutional registry study
The goals of this undertaking were to assess the outcomes of thyroid screening tests and adherence to thyroid screening guidelines across five Down syndrome (DS) specialty clinics in various states. Data related to thyroid screening were collected for 663 individuals across five clinics specializing in the comprehensive care of individuals with DS for a period of 1 year. Of the 663 participants, 47.7% of participants had a TSH and free T4 ordered at their DS specialty clinic visit. Approximately 19.0% (60/316) had a new thyroid disorder diagnosis made. We conclude that a sizable proportion of the patients with DS are not u...
Source: American Journal of Medical Genetics Part A - March 23, 2017 Category: Genetics & Stem Cells Authors: Jenifer Lavigne, Christianne Sharr, Ibrahim Elsharkawi, Al Ozonoff, Nicole Baumer, Campbell Brasington, Sheila Cannon, Blythe Crissman, Emily Davidson, Jose C. Florez, Priya Kishnani, Angela Lombardo, Jordan Lyerly, Mary Ellen McDonough, Alison Schwartz, Tags: ORIGINAL ARTICLE Source Type: research

Intrafamilial phenotypic variability in a Polish family with Sensenbrenner syndrome and biallelic WDR35 mutations
We present a detailed clinical descriptions of two female siblings showing an intrafamilial phenotypic variability of the disease, and illustrating the potential lethality of CED. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 23, 2017 Category: Genetics & Stem Cells Authors: Joanna Walczak ‐Sztulpa, Anna Wawrocka, Agata Sobierajewicz, Lukasz Kuszel, Jan Zawadzki, Ryszard Grenda, Anna Swiader‐Lesniak, Beata Kocyla‐Karczmarewicz, Anna Wnuk, Anna Latos‐Bielenska, Krystyna H. Chrzanowska Tags: CLINICAL REPORT Source Type: research

An Xq22.1q22.2 nullisomy in a male patient with severe neurological impairment
In this study, we identified the first case of a male patient associated with an Xq22 nullisomy in a region proximal to PLP1. The patient showed severe neurological impairment and was bedridden. Brain magnetic resonance imaging revealed a severely reduced cerebral volume. The chromosomal region proximal to PLP1 was considered to be significantly important for brain development. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Kentaro Shirai, Yuya Higashi, Keiko Shimojima, Toshiyuki Yamamoto Tags: CLINICAL REPORT Source Type: research

Recessive mutations in SLC35A3 cause early onset epileptic encephalopathy with skeletal defects
We describe the clinical and whole genome sequencing (WGS) study of a non‐consanguineous Italian family in which two siblings, a boy and a girl, manifesting a severe epileptic encephalopathy (EE) with skeletal abnormalities, carried novel SLC35A3 compound heterozygous mutations. Both siblings exhibited infantile spasms, associated with focal, and tonic vibratory seizures from early infancy. EEG recordings showed a suppression‐burst (SB) pattern and multifocal paroxysmal activity in both. In addition both had quadriplegia, acquired microcephaly, and severe intellectual disability. General examination showed distal arthr...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Carla Marini, Katia Hardies, Tiziana Pisano, Patrick May, Sarah Weckhuysen, Elena Cellini, Arvid Suls, Davide Mei, Rudi Balling, Peter D. Jonghe, Ingo Helbig, Domenico Garozzo, , Renzo Guerrini Tags: CLINICAL REPORT Source Type: research

A novel patient with an attenuated Costello syndrome phenotype due to an HRAS mutation affecting codon 146 —Literature review and update
We report on a patient with de novo missense mutation causing an amino acid change at codon 146 of HRAS, c.436G > C:p.Ala146Pro, who presented with subtle dysmorphic features, failure to thrive, global developmental delay, and hypertrophic obstructive cardiomyopathy. Mutations affecting codon 146 are observed in
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Annie Ting Gee Chiu, Gordon Ka ‐Chun Leung, Yoyo Wing‐Yiu Chu, Karen W. Gripp, Brian Hon‐Yin Chung Tags: CLINICAL REPORT Source Type: research

Confirmation of CAGSSS syndrome as a distinct entity in a Danish patient with a novel homozygous mutation in IARS2
We present her clinical features and particularly highlight her skeletal findings, which confirm the presence of a primary SEMD skeletal dysplasia in a growing list of mitochondrial‐related disorders including CAGSSS, CODAS, EVEN‐PLUS, and X‐linked SEMD‐MR syndromes. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Shahida Moosa, Annette Haagerup, Pernille Axel Gregersen, Karin Kastberg Petersen, Janine Altm üller, Holger Thiele, Peter Nürnberg, Tae‐Joon Cho, Ok‐Hwa Kim, Gen Nishimura, Bernd Wollnik, Ida Vogel Tags: CLINICAL REPORT Source Type: research

Turner syndrome ‐specific and general population Z‐scores are equivalent for most adults with Turner syndrome
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Siddharth Prakash, , Dianna Milewicz Tags: Correspondence Source Type: research

Novel clinical findings in the first Egyptian case of Sotos syndrome caused by complete deletion of the NSD1 gene
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Ebtesam Abdalla, Oliver Bartsch, Danuta Galetzka, Ulrich Zechner Tags: Research Letter Source Type: research

A 590 kb deletion caused by non ‐allelic homologous recombination between two LINE‐1 elements in a patient with mesomelia‐synostosis syndrome
Mesomelia‐synostoses syndrome (MSS) is a rare, autosomal‐dominant, syndromal osteochondrodysplasia characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations due to a non‐recurrent deletion at 8q13 that always encompasses two coding‐genes, SULF1 and SLCO5A1. To date, five unrelated patients have been reported worldwide, and MMS was previously proposed to not be a genomic disorder associated with deletions recurring from non‐allelic homologous recombination (NAHR) in at least two analyzed cases. We conducted targeted gene panel sequencing and subsequent array‐based copy n...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Tomohiro Kohmoto, Takuya Naruto, Miki Watanabe, Yuji Fujita, Sae Ujiro, Nana Okamoto, Hideaki Horikawa, Kiyoshi Masuda, Issei Imoto Tags: CLINICAL REPORT Source Type: research

Long term survival of a patient with Perlman syndrome due to novel compound heterozygous missense mutations in RNB domain of DIS3L2
Perlman syndrome is a rare overgrowth syndrome characterized by polyhydramnios, macrosomia, distinctive facial appearance, renal dysplasia, and a predisposition to Wilms’ tumor. The syndrome is often associated with a high neonatal mortality rate and there are few reports of long‐term survivors. We studied a 6‐year‐old Japanese female patient, who was diagnosed with Perlman syndrome, with novel compound heterozygous mutations in DIS3L2 (c.[367‐2A > G];[1328T > A]), who has survived long term. Most reported DIS3L2 mutations have been the homozygous deletion of exon 6 or exon 9...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Noriko Soma, Ken Higashimoto, Masaru Imamura, Akihiko Saitoh, Hidenobu Soejima, Keisuke Nagasaki Tags: CLINICAL REPORT Source Type: research

22q11.2q13 duplication including SOX10 causes sex ‐reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease
We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149–151], of an individual with 22q duplication and sex‐reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Nadia Falah, Jennifer E. Posey, Willa Thorson, Paul Benke, Mustafa Tekin, Brocha Tarshish, James R. Lupski, Tamar Harel Tags: CLINICAL REPORT Source Type: research

Noonan syndrome, PTPN11 mutations, and brain tumors. A clinical report and review of the literature
This report provides further support for the relation of DNTs with RASopathies and for the implication of RAS/MAPK pathways in sporadic low‐grade glial tumors including DNTs. © 2017 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Aurore Siegfried, Claude Cances, Marie Denuelle, Najat Loukh, Ma ïté Tauber, Hélène Cavé, Marie‐Bernadette Delisle Tags: Clinical Report Source Type: research

Partial tetrasomy 11q resulting from an intrachromosomal triplication of a 22 Mb region of chromosome 11
We describe a female patient harboring an intrachromosomal triplication who presented to the Genetics clinic with dysmorphic features, including telecanthus, flat facial profile, and prognathism, short stature, widely spaced nipples, multiple allergy complaints, loose bowel movements, and mild speech delay. Microarray analysis showed a copy number gain of a 22.37 Mb region of chromosome 11 between bands 11q14.1 and 11q22.1. This region contains 95 genes and seven microRNAs, none of which have been implicated in a disease resulting from increased gene dosage. FISH analysis using a probe targeted to the middle of the segment...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Mariana Kekis, Carol Deeg, Sayaka Hashimoto, Aimee McKinney, Linda Erdman, Cecelia Green ‐Geer, Christine Shuss, Scott Hickey, Caroline Astbury, Robert E. Pyatt Tags: Clinical Report Source Type: research

Homozygous mutation in PTRH2 gene causes progressive sensorineural deafness and peripheral neuropathy
PTRH2 is an evolutionarily highly conserved mitochondrial protein that belongs to a family of peptidyl‐tRNA hydrolases. Recently, patients from two consanguineous families with mutations in the PTRH2 gene were reported. Global developmental delay associated with microcephaly, growth retardation, progressive ataxia, distal muscle weakness with ankle contractures, demyelinating sensorimotor neuropathy, and sensorineural hearing loss were present in all patients, while facial dysmorphism with widely spaced eyes, exotropia, thin upper lip, proximally placed thumbs, and deformities of the fingers and toes were present in some...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Rajech Sharkia, Stavit A. Shalev, Abdelnaser Zalan, Milit Marom ‐David, Nathan Watemberg, Jill E. Urquhart, Sarah B. Daly, Sanjeev S. Bhaskar, Simon G. Williams, William G. Newman, Ronen Spiegel, Abdussalam Azem, Orly Elpeleg, Muhammad Mahajnah Tags: CLINICAL REPORT Source Type: research

Association of NPC1 variant p.P237S with a pathogenic splice variant in two Niemann –Pick disease type C1 patients
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Alexander Salman, Antony Cougnoux, Nicole Farhat, Christopher A. Wassif, Forbes D. Porter Tags: Research Letter Source Type: research

Exome sequencing identifies novel NTRK1 mutations in patients with HSAN ‐IV phenotype
Hereditary sensory autonomic neuropathy type IV (HSAN‐IV) is a rare autosomal recessive disorder that usually begins in infancy and is characterized by anhidrosis, insensitivity to noxious stimuli leading to self‐mutilating behavior, and intellectual disability. HSAN‐IV is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene, NTRK1, encoding the high‐affinity receptor of nerve growth factor (NGF) which maps to chromosome 1q21‐q22. Patients with HSAN‐IV lack all NGF‐dependent neurons, the primary afferents and sympathetic postganglionic neurons leading to lack of pain sensation and the ...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Ruqaiah Altassan, Haya Al Saud, Tariq Ahmad Masoodi, Haya Al Dosssari, Ola Khalifa, Hamad Al ‐Zaidan, Nadia Sakati, Zuhair Rhabeeni, Zuhair Al‐Hassnan, Yousef Binamer, Nadia Alhashemi, William Wade, Zayed Al‐Zayed, Moeen Al‐Sayed, Mohamed A. Al‐ Tags: ORIGINAL ARTICLE Source Type: research

Somatic PIK3CA mutations in seven patients with PIK3CA ‐related overgrowth spectrum
Somatic mutations in PIK3CA cause many overgrowth syndromes that have been recently coined the “PIK3CA‐Related Overgrowth Spectrum.” Here, we present seven molecularly confirmed patients with PIK3CA‐Related Overgrowth Spectrum, including patients with Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal syndrome, Klippel–Trenaunay syndrome, lymphatic malformation and two with atypical phenotypes that cannot be classified into existing disease categories. The literature on PIK3CA‐Related Overgrowth Spectrum, suggests that PIK3CA c.1258T>C; p.(Cys4...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Kit San Yeung, Janice Jing Kun Ip, Chin Pang Chow, Evelyn Yue Ling Kuong, Paul Kwong ‐Hang Tam, Godfrey Chi‐Fung Chan, Brian Hon‐Yin Chung Tags: Original Article Source Type: research

Quantitative phenotypic and network analysis of 1q44 microdeletion for microcephaly
We report a case of a de novo 1q44 deletion in an 8‐year‐old boy with microcephaly in whom AKT3 is not deleted. We used a systematic review of the literature, our patient, and network analysis to gain a better understanding of the genetic basis of microcephaly in 1q deletion patients. Our analysis showed that while AKT3 deletion is associated with more severe (≤3 SD) microcephaly in 1q43‐q44 deletion patients, other genes may contribute to microcephaly in AKT3 intact patients with microcephaly and 1q43‐44 deletion syndrome. We identified a potential role for HNRNPU, SMYD3, NLRP3, and KIF26B in microcephal...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Nicholas Raun, Janette Mailo, Egidio Spinelli, Xu He, Sarah McAvena, Logan Brand, Julia O'Sullivan, John Andersen, Lawrence Richer, Richard Tang ‐Wai, Francois V. Bolduc Tags: ORIGINAL ARTICLE Source Type: research

Two patients with the heterozygous R189H mutation in ACTA2 and Complex congenital heart defects expands the cardiac phenotype of multisystemic smooth muscle dysfunction syndrome
We describe two patients, a 3‐day‐old newborn and a 26‐year‐old woman, with this unique mutation in association with a huge PDA and an aorto‐pulmonary window. In addition, one showed a coarctation of the aortic arch and the other a complete interruption of the aortic arch type A; thereby expanding the spectrum of cardiac congenital heart defect of this syndrome. Each patient displayed a huge PDA and an extra‐cardiovascular phenotype consistent with MSMDS. These observations exemplify that a functional alpha 2 smooth muscle actin is necessary for proper cardiovascular organ development, and demonstrate that a ve...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Thushiha Logeswaran, Christoph Friedburg, Karoline Hofmann, Hakan Akintuerk, Saskia Biskup, Michael Graef, Ali Rad, Axel Weber, Bernd A. Neubauer, Dietmar Schranz, Patrice Bouvagnet, Birgit Lorenz, Andreas Hahn Tags: Original Article Source Type: research

Revised estimates of the risk of fetal loss following a prenatal diagnosis of trisomy 13 or trisomy 18
Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13) both have high natural fetal loss rates. The aim of this study was to provide estimates of these fetal loss rates by single gestational week of age using data from the National Down Syndrome Cytogenetic Register. Data from all pregnancies with Edwards or Patau syndrome that were prenatally detected in England and Wales from 2004 to 2014 was analyzed using Kaplan‐Meier survival estimates. Pregnancies were entered into the analysis at the time of gestation at diagnosis, and were considered “under observation” until the gestation at outcome. There wer...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Alana Cavadino, Joan K. Morris Tags: ORIGINAL ARTICLE Source Type: research

Brain morphology in children with nevoid basal cell carcinoma syndrome
Brain morphology is tightly regulated by diverse signaling pathways. Hedgehog signaling is a candidate pathway considered responsible for regulating brain morphology. Nevoid basal cell carcinoma syndrome (NBCCS), caused by a PTCH1 mutation in the hedgehog signaling pathway, occasionally exhibits macrocephaly and medulloblastoma. Although cerebellar enlargement occurs in ptch1 heterozygous‐deficient mice, its impact on human brain development remains unknown. We investigated the brain morphological characteristics of children with NBCCS. We evaluated brain T1‐weighted images from nine children with NBCCS and 15 age‐ma...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Tadashi Shiohama, Katsunori Fujii, Toshiyuki Miyashita, Hiromi Mizuochi, Hideki Uchikawa, Naoki Shimojo Tags: ORIGINAL ARTICLE Source Type: research

Targeted molecular investigation in patients within the clinical spectrum of Auriculocondylar syndrome
Auriculocondylar syndrome, mainly characterized by micrognathia, small mandibular condyle, and question mark ears, is a rare disease segregating in an autosomal dominant pattern in the majority of the families reported in the literature. So far, pathogenic variants in PLCB4, GNAI3, and EDN1 have been associated with this syndrome. It is caused by a developmental abnormality of the first and second pharyngeal arches and it is associated with great inter‐ and intra‐familial clinical variability, with some patients not presenting the typical phenotype of the syndrome. Moreover, only a few patients of each molecular subtyp...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Vanessa L. Romanelli Tavares, Roseli M. Zechi ‐Ceide, Debora R. Bertola, Christopher T. Gordon, Simone G. Ferreira, Gabriella S. P. Hsia, Guilherme L. Yamamoto, Suzana A. M. Ezquina, Nancy M. Kokitsu‐Nakata, Siulan Vendramini‐Pittoli, Renato S. Frei Tags: Original Article Source Type: research

A qualitative study of adolescents ’ understanding of biobanks and their attitudes toward participation, re‐contact, and data sharing
While biobanks have become more prevalent, little is known about adolescents’ views of key governance issues. We conducted semi‐structured interviews with adolescents between 15 and 17 years old to solicit their views. All interviews were audiotaped and transcribed. Two investigators coded the transcripts and resolved any discrepancies through consensus. We conducted 18 interviews before reaching data saturation. Four participants (22%) had previously heard of a biobank. Many participants had misunderstandings about biobanks, some of which persisted after education. Participants believed that enrolling in a biobank...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Andrea M. Murad, Melanie F. Myers, Susan D. Thompson, Rachel Fisher, Armand H. Matheny Antommaria Tags: ORIGINAL ARTICLE Source Type: research

22q11.2 deletion syndrome in diverse populations
In this study, individuals from diverse populations with 22q11.2 DS were evaluated clinically and by facial analysis technology. Clinical information from 106 individuals and images from 101 were collected from individuals with 22q11.2 DS from 11 countries; average age was 11.7 and 47% were male. Individuals were grouped into categories of African descent (African), Asian, and Latin American. We found that the phenotype of 22q11.2 DS varied across population groups. Only two findings, congenital heart disease and learning problems, were found in greater than 50% of participants. When comparing the clinical features of 22q1...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Paul Kruszka, Yonit A. Addissie, Daniel E. McGinn, Antonio R. Porras, Elijah Biggs, Matthew Share, T. Blaine Crowley, Brian H. Y. Chung, Gary T. K. Mok, Christopher C. Y. Mak, Premala Muthukumarasamy, Meow ‐Keong Thong, Nirmala D. Sirisena, Vajira H. W. Tags: ORIGINAL ARTICLE Source Type: research

The phenotypic spectrum of congenital Zika syndrome
This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM‐ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger co...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Miguel del Campo, Ian M. L. Feitosa, Erlane M. Ribeiro, Dafne D. G. Horovitz, Andr é L. S. Pessoa, Giovanny V. A. França, Alfredo García‐Alix, Maria J. R. Doriqui, Hector Y. C. Wanderley, Maria V. T. Sanseverino, João I. C. F. Neri, João M. Pina‐ Tags: ORIGINAL ARTICLE Source Type: research

In this issue
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Tags: the AJMG SEQUENCE: Decoding News and Trends for the Medical Genetics Community by Deborah Levenson Source Type: research

Lawsuit raises questions about variant interpretation and communication
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Tags: the AJMG SEQUENCE: Decoding News and Trends for the Medical Genetics Community by Deborah Levenson Source Type: research

First drug to treat spinal muscular atrophy gets FDA approval
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Tags: the AJMG SEQUENCE: Decoding News and Trends for the Medical Genetics Community by Deborah Levenson Source Type: research

Publication schedule for 2017
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Tags: Issue Information Source Type: research

Table of Contents, Volume 173A, Number 4, April 2017
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Tags: Issue Information Source Type: research

Cover Image, Volume 173A, Number 4, April 2017
The cover image, by Paul Kruszka et al., is based on the Original Article 22q11.2 deletion syndrome in diverse populations, DOI: 10.1002/ajmg.a.38199. Individual images are property of the National Human Genome Research Institute and are in the public domain. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Paul Kruszka, Yonit A. Addissie, Daniel E. McGinn, Antonio R. Porras, Elijah Biggs, Matthew Share, T. Blaine Crowley, Brian H. Y. Chung, Gary T. K. Mok, Christopher C. Y. Mak, Premala Muthukumarasamy, Meow ‐Keong Thong, Nirmala D. Sirisena, Vajira H. W. Tags: Cover Image Source Type: research

Mystery solved: Our son's autism and extreme self ‐injury is genetic and treatable
Our 17‐year‐old autistic son Jake is declining at the same rate his peers are developing. He has the pimples, the sudden height, and the hormones. But the right side of his body slumps like someone who has had a stroke. Once right handed, he now uses only his left hand. At 15, he knocked his eyes off their parallel tracks by slamming his temple into the corner of a wooden post. One eye looks straight ahead while the other looks up and to the side. Both optic nerves are damaged. All the damage is self‐inflicted. He has been banging and punching his head since babyhood. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 20, 2017 Category: Genetics & Stem Cells Authors: Tanja Bartel Tags: FRAMESHIFT Source Type: research

Multigenerational pedigree with STAR syndrome: A novel FAM58A variant and expansion of the phenotype
STAR syndrome is a rare X‐linked dominant disorder characterized by toe Syndactyly, Telecanthus, Anogenital malformations, and Renal malformations, and is caused by loss‐of‐function variants in FAM58A. Our proband presented with the hallmark features of STAR syndrome, as well as some additional less typical features including tethered cord and hearing loss. The proband's mother and maternal half‐sister had similar clinical histories, but had variability in phenotypic severity. Clinical whole exome sequencing revealed a novel pathogenic nonsense variant, c.651G>A (p.Trp217X; NM_152274), in FAM58A in the proband, ...
Source: American Journal of Medical Genetics Part A - March 20, 2017 Category: Genetics & Stem Cells Authors: Nicole J. Boczek, Teresa Kruisselbrink, Margot A. Cousin, Patrick R. Blackburn, Eric W. Klee, Ralitza H. Gavrilova, Brendan C. Lanpher Tags: CLINICAL REPORT Source Type: research

A novel aberrant splice site mutation in COL27A1 is responsible for Steel syndrome and extension of the phenotype to include hearing loss
In this study, we identified a novel homozygous splice site variant in COL27A1 (c.3556‐2A>G) in a consanguineous Emirati family with a child affected by Steel syndrome. In addition, the affected child had severe non‐progressive sensorineural hearing loss not reported previously. The variant segregated in the family in an autosomal recessive manner and we show that the variant alters mRNA splicing. Furthermore, relative quantitative analysis revealed a marked reduction in gene expression in the proposita compared to healthy controls. Segregation analysis of heterozygous variants, related to hearing loss, identified b...
Source: American Journal of Medical Genetics Part A - March 20, 2017 Category: Genetics & Stem Cells Authors: Nesrin Gariballa, Afif Ben ‐Mahmoud, Makanko Komara, Aisha M. Al‐Shamsi, Anne John, Bassam R. Ali, Lihadh Al‐Gazali Tags: ORIGINAL ARTICLE Source Type: research

Novel compound heterozygous mutations in BCS1L gene causing Bjornstad syndrome in two siblings
We report the first Italian patients with Bjornstad syndrome, two siblings with pili torti and sensorineural hearing loss, in whom we detected two novel compound heterozygous mutations in BCS1L. A thorough clinical evaluation did not reveal any features consistent with complex III deficiency or GRACILE syndrome. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 20, 2017 Category: Genetics & Stem Cells Authors: Mariateresa Falco, Annamaria Franz è, Sandra Iossa, Luigia De Falco, Antonella Gambale, Elio Marciano, Achille Iolascon Tags: CLINICAL REPORT Source Type: research

The association of maternal lymphatic markers and critical congenital heart defects in the fetus —A population based case‐control study
In this study, increased mid‐pregnancy maternal serum levels of PDGF AA were associated with CCHDs in offspring. The highest PDGF AA levels were found in mothers of fetuses with HLHS. These findings may be useful in screening for CCHDs and offer insight into their association with nuchal translucency. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 20, 2017 Category: Genetics & Stem Cells Authors: Martina A. Steurer, Mary E. Norton, Rebecca J. Baer, Gary M. Shaw, Sheila Keating, Anita J. Moon ‐Grady, Christina D. Chambers, Laura L. Jelliffe‐Pawlowski Tags: ORIGINAL ARTICLE Source Type: research

Developmental biology, 11th edition 2016
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 19, 2017 Category: Genetics & Stem Cells Authors: S. F. Gilbert, M. J. F. Barresi Tags: BOOK REVIEW Source Type: research

Maxillofacial features and systemic malformations in expanded spectrum Hemifacial Microsomia
Hemifacial microsomia (HFM) is a rare, multisystemic congenital disease with estimated frequency of 1/26370 births in Europe. Most cases are sporadic and caused by unilateral abnormal morphogenesis of the first and second pharyngeal arches. The aim of this study is to define the types and frequency of maxillofacial and systemic malformations in HFM patients. This is a case series study of patients with HFM evaluated at a single institution. Data were acquired through history, physical examination, photographs, diagnostic radiology, and laboratory and analyzed by the FileMakerPro database on 95 patients (54F; 41M) of which ...
Source: American Journal of Medical Genetics Part A - March 19, 2017 Category: Genetics & Stem Cells Authors: Noah Cohen, Erica Cohen, Alberto Gaiero, Silvia Zecca, Graziella Fichera, Federica Baldi, Joseph Felix Giordanetto, Jacques Marie Mercier, Amnon Cohen Tags: ORIGINAL ARTICLE Source Type: research

Adding value to genetic testing through utilization management: Commercial laboratory's experience
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 19, 2017 Category: Genetics & Stem Cells Authors: Gina K. Londre, Christina A. Zaleski, Jessie H. Conta Tags: RESEARCH LETTER Source Type: research

Thomas H. Shepard, M.D., pioneer in embryology and teratology
Dr. Thomas H. Shepard died on October 3, 2016 at the age of 93. He was a major figure in the fields of teratology, embryonic and fetal pathology, and pediatrics. He was beloved by his colleagues as he was by the many students and fellows whom he taught, mentored and befriended. His contributions to teratology are extraordinary and he is greatly missed. © 2017 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 19, 2017 Category: Genetics & Stem Cells Authors: Alan G. Fantel, Janine E. Polifka, Godfrey P. Oakley Tags: IN MEMORIAM Source Type: research

Maternal uniparental disomy of chromosome 15 and concomitant STRC and CATSPER2 deletion ‐mediated deafness‐infertility syndrome
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 19, 2017 Category: Genetics & Stem Cells Authors: Lisa Karger, Wahab A. Khan, Rafaela Calabio, Ram Singh, Bixia Xiang, Arvind Babu, Ninette Cohen, Amy C. Yang, Stuart A. Scott Tags: RESEARCH LETTER Source Type: research

Oculo –facio–cardio–dental syndrome with craniosynostosis, temporal hypertrichosis, and deafness
We report the case of a 7‐month‐old girl with atypical oculo–facio–cardio–dental syndrome (OFCD). A novel de novo pathogenic mutation in the BCL6 interacting co‐repressor gene (BCOR) (c.4540C>T; p.Arg1514*), was identified on the X chromosome. This case expands the phenotype of OFCD as it is the first report of a case presenting with craniosynostois, temporal hypertrichosis, supraorbital grooving, and underdevelopment of the midface. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 19, 2017 Category: Genetics & Stem Cells Authors: James J. O'Byrne, Eoghan Laffan, Dylan J. Murray, William Reardon Tags: CLINICAL REPORT Source Type: research

The outcomes of 31 cases of trisomy 13 diagnosed in utero with various management options
There are few reports on the prognosis of prenatally diagnosed trisomy 13 in relation to postnatal management. The aim of this study was to report on the prenatal and postnatal outcomes and postnatal management of trisomy 13 fetuses that were prenatally diagnosed at our center between 2003 and 2015. The data were retrospectively reviewed from medical records. Of the 31 cases of trisomy 13, 12 patients were diagnosed before 22 weeks of gestation, and 19 were diagnosed at or after 22 weeks of gestation. Nine families opted for termination of the pregnancy, 14 fetuses died, and 8 were born alive. Aggressive treatment was requ...
Source: American Journal of Medical Genetics Part A - March 6, 2017 Category: Genetics & Stem Cells Authors: Ken Takahashi, Aiko Sasaki, Seiji Wada, Yuka Wada, Keiko Tsukamoto, Rika Kosaki, Yushi Ito, Haruhiko Sago Tags: ORIGINAL ARTICLE Source Type: research

Refining patterns of joint hypermobility, habitus, and orthopedic traits in joint hypermobility syndrome and Ehlers –Danlos syndrome, hypermobility type
This study pointed out a more protean musculoskeletal phenotype than previously considered according to available diagnostic criteria for JHS/EDS–HT. Our findings corroborated the need for a re‐thinking of JHS/EDS–HT on clinical grounds in order to find better therapeutic and research strategies. © 2017 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 6, 2017 Category: Genetics & Stem Cells Authors: Silvia Morlino, Chiara Dordoni, Isabella Sperduti, Marina Venturini, Claudia Celletti, Filippo Camerota, Marina Colombi, Marco Castori Tags: Original Article Source Type: research

Interrupted/bipartite clavicle as a diagnostic clue in Kabuki syndrome
We report two patients’ presentation of Kabuki syndrome caused by different KMT2D mutations, both including an interrupted/bipartite clavicle. The clinical diagnosis of Kabuki syndrome may be challenging, especially in younger patients and we suggest that the observation of a bipartite clavicle may be an additional diagnostic clue to prompt investigation for Kabuki syndrome. We also hypothesize that bipartite/pseudofractured clavicles or other skeletal defects may be under‐recognized features of the clinical presentation of the chromatin remodeling disorders. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - March 2, 2017 Category: Genetics & Stem Cells Authors: Maria Haanp ää, Helena Schlecht, Gauri Batra, Jill Clayton‐Smith, Sofia Douzgou Tags: CLINICAL REPORT Source Type: research

The HHID syndrome of hypertrichosis, hyperkeratosis, abnormal corpus callosum, intellectual disability, and minor anomalies is caused by mutations in ARID1B
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 28, 2017 Category: Genetics & Stem Cells Authors: Markus Zweier, Maarit M. Peippo, Minna P öyhönen, Helena Kääriäinen, Anaïs Begemann, Pascal Joset, Beatrice Oneda, Anita Rauch Tags: RESEARCH LETTER Source Type: research

Further evidence for specific IFIH1 mutation as a cause of Singleton –Merten syndrome with phenotypic heterogeneity
Singleton–Merten syndrome (MIM 182250) is an autosomal dominant inherited disorder characterized by early onset periodontitis, root resorption, osteopenia, osteoporosis, and aortic valve or thoracic aorta calcification. The disorder can have significant intrafamilial phenotypic variability. Here, we present a mother and daughter with Singleton–Merten syndrome harboring a previously described pathogenic missense mutation, c.2465G>A p.(Arg822Gln), in IFIH1 (interferon induced with helicase C domain 1), encoding MDA5 (Melanoma Differentiation‐Associated protein 5). These data confirm the pathogenicity of IFIH...
Source: American Journal of Medical Genetics Part A - February 28, 2017 Category: Genetics & Stem Cells Authors: Maria Pettersson, Birgitta Bergendal, Johanna Norderyd, Daniel Nilsson, Britt ‐Marie Anderlid, Ann Nordgren, Anna Lindstrand Tags: CLINICAL REPORT Source Type: research

De novo loss ‐of‐function variants in STAG2 are associated with developmental delay, microcephaly, and congenital anomalies
The cohesin complex is an evolutionarily conserved multi‐subunit protein complex which regulates sister chromatid cohesion during mitosis and meiosis. Additionally, the cohesin complex regulates DNA replication, DNA repair, and transcription. The core of the complex consists of four subunits: SMC1A, SMC3, RAD21, and STAG1/2. Loss‐of‐function mutations in many of these proteins have been implicated in human developmental disorders collectively termed “cohesinopathies.” Through clinical exome sequencing (CES) of an 8‐year‐old girl with a clinical history of global developmental delay, microcephaly, micr...
Source: American Journal of Medical Genetics Part A - February 28, 2017 Category: Genetics & Stem Cells Authors: Sureni V. Mullegama, Steven D. Klein, Milene V. Mulatinho, Tharanga Niroshini Senaratne, Kathryn Singh, , Dzung C. Nguyen, Natalie M. Gallant, Samuel P. Strom, Shahnaz Ghahremani, Nagesh P. Rao, Julian A. Martinez ‐Agosto Tags: ORIGINAL ARTICLE Source Type: research

In Memoriam: Laurence E. karp (1939 –2016)
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 28, 2017 Category: Genetics & Stem Cells Authors: Robert G. Resta Tags: IN MEMORIAM Source Type: research

Tissue ‐specific mosaicism for a lethal osteogenesis imperfecta COL1A1 mutation causes mild OI/EDS overlap syndrome
We describe a patient with clinical signs of Ehlers–Danlos syndrome (EDS), including fragile skin, easy bruising, recurrent luxations, and fractures resembling mild OI. Biochemical collagen analysis of the patients’ dermal fibroblasts showed faint overmodification of the type I collagen bands, a finding specific for structural defects in type I collagen. Bidirectional Sanger sequencing detected an in‐frame deletion in exon 44 of COL1A1 (c.3150_3158del), resulting in the deletion of three amino acids (p.Ala1053_Gly1055del) in the collagen triple helix. This COL1A1 mutation was hitherto identified in four proba...
Source: American Journal of Medical Genetics Part A - February 28, 2017 Category: Genetics & Stem Cells Authors: Sofie Symoens, Wouter Steyaert, Lynn Demuynck, Anne De Paepe, Karin E. M. Diderich, Fransiska Malfait, Paul J. Coucke Tags: CLINICAL REPORT Source Type: research