Somatic mosaic deletions involving SCN1A cause Dravet syndrome
This study reinforces the importance of somatic mosaicism caused by copy number variations in disease‐causing genes, and provides an alternative spectrum of SCN1A mutations causative of DS. Somatic deletions in SCN1A should be considered in cases with DS when standard screenings for SCN1A mutations are apparently negative for mutations. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - January 17, 2018 Category: Genetics & Stem Cells Authors: Tojo Nakayama, Atsushi Ishii, Takeshi Yoshida, Hirosato Nasu, Keiko Shimojima, Toshiyuki Yamamoto, Shigeo Kure, Shinichi Hirose Tags: CLINICAL REPORT Source Type: research

Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient with non ‐lethal form of Raine syndrome
Raine syndrome is a rare osteosclerotic bone dysplasia characterized by craniofacial anomalies and intracranial calcification. Most patients with Raine syndrome are of Arab ancestry and die during the neonatal period. We herein report a Japanese patient with non‐lethal Raine syndrome who presented with characteristic cerebral hyperechogenicity and a hypoplastic nose by fetal ultrasonography. She was admitted to the NICU due to pyriform aperture stenosis. Craniofacial abnormalities, intracranial calcification, osteosclerosis, chondrodysplasia punctata, and a mutation of FAM20C was identified. She was subsequently discharg...
Source: American Journal of Medical Genetics Part A - January 17, 2018 Category: Genetics & Stem Cells Authors: Kei Tamai, Katsuhiko Tada, Akihito Takeuchi, Makoto Nakamura, Hidenori Marunaka, Yosuke Washio, Hiroyuki Tanaka, Fuyuki Miya, Nobuhiko Okamoto, Misao Kageyama Tags: CLINICAL REPORT Source Type: research

Thoracic aortic aneurysm in patients with loss of function Filamin A mutations: Clinical characterization, genetics, and recommendations
The frequency and gender distribution of thoracic aortic aneurysm as a cardiovascular manifestation of loss‐of‐function (LOF) X‐linked FilaminA (FLNA) mutations are not known. Furthermore, there is very limited cardiovascular morbidity or mortality data in children and adults. We analyzed cardiac data on the largest series of 114 patients with LOF FLNA mutations, both children and adults, with periventricular nodular heterotopia (PVNH), including 48 study patients and 66 literature patients, median age of 22.0 years (88 F, 26 M, range: 0–71 years), with 75 FLNA mutations observed in 80 families. M...
Source: American Journal of Medical Genetics Part A - January 15, 2018 Category: Genetics & Stem Cells Authors: Ming Hui Chen, Sangita Choudhury, Mami Hirata, Siri Khalsa, Bernard Chang, Christopher A. Walsh 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 - January 15, 2018 Category: Genetics & Stem Cells Tags: the AJMG SEQUENCE: Decoding News and Trends for the Medical Genetics Community by Deborah Levenson Source Type: research

Reanalysis of clinical whole ‐exome sequence data yields multiple new diagnoses
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - January 15, 2018 Category: Genetics & Stem Cells Tags: the AJMG SEQUENCE: Decoding News and Trends for the Medical Genetics Community by Deborah Levenson Source Type: research

GTEx project maps wide range of normal human genetic variation
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - January 15, 2018 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 2018
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - January 15, 2018 Category: Genetics & Stem Cells Tags: ISSUE INFORMATION Source Type: research

Table of Contents, Volume 176A, Number 2, February 2018
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - January 15, 2018 Category: Genetics & Stem Cells Tags: ISSUE INFORMATION Source Type: research

Cover Image, Volume 176A, Number 2, February 2018
The cover image, by Ming Hui Chen et al., is based on the Original Article Thoracic Aortic Aneurysm in Patients with Loss of Function Filamin A Mutations: Clinical Characterization, Genetics, and Recommendations, DOI: 10.1002/ajmg.a.38580. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - January 15, 2018 Category: Genetics & Stem Cells Authors: Ming Hui Chen, Sangita Choudhury, Mami Hirata, Siri Khalsa, Bernard Chang, Christopher A. Walsh Tags: COVER IMAGE Source Type: research

---
American Journal of Medical Genetics Part A,Volume 176, Issue 3, Page 687-691, March 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - January 13, 2018 Category: Genetics & Stem Cells Source Type: research

---
American Journal of Medical Genetics Part A,Volume 176, Issue 3, Page 663-667, March 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - January 5, 2018 Category: Genetics & Stem Cells Source Type: research

Spectrum of bone marrow pathology and hematological abnormalities in methylmalonic acidemia
This report emphasizes the need for bone marrow examination in these patients with refractory or unexplained severe cytopenia, to confirm bone marrow pathology, and to rule out other diseases with similar clinical presentation for a better clinical outcome. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - January 1, 2018 Category: Genetics & Stem Cells Authors: Nasir A. Bakshi, Talal Al ‐Anzi, Said Y. Mohamed, Zuhair Rahbeeni, Moeen AlSayed, Mohammed Al‐Owain, Raashda A. Sulaiman Tags: CLINICAL REPORT Source Type: research

A novel pathogenic MYH3 mutation in a child with Sheldon –Hall syndrome and vertebral fusions
We report the case of a boy with a novel pathogenic MYH3 mutation, presenting with the classical clinical features of SHS in association with unilateral carpal bone fusion and multiple vertebral fusions. This distinctive phenotype has never been reported in the literature so far and expands the phenotypic spectrum of SHS, endorsing the clinical variability of patients with MYH3‐related disorders. Our findings also support a role for MYH3 in both muscle and bone development, suggesting a phenotypic continuum in MYH3‐related disorders. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - January 1, 2018 Category: Genetics & Stem Cells Authors: Marcello Scala, Andrea Accogli, Elisa De Grandis, Anna Allegri, Christoph P. Bagowski, Moneef Shoukier, Mohamad Maghnie, Valeria Capra Tags: CLINICAL REPORT Source Type: research

UBE2A deficiency in two siblings: A novel splicing variant inherited from a maternal germline mosaicism
UBE2A deficiency is a syndromic condition of X‐linked intellectual disability (ID) characterized by typical dysmorphic features that include synophrys, prominent supraorbital ridges, almond‐shaped, and deep‐set eyes, large ears, wide mouth, myxedematous appearance, hirsutism, micropenis, and onychodystrophy. To date, only seven familial UBE2A intragenic mutations and nine larger microdeletions encompassing UBE2A have been reported. Here, we describe two siblings with X‐linked ID and typical clinical features of UBE2A deficiency caused by a novel hemizygous variant, identified by massively parallel sequencing of X...
Source: American Journal of Medical Genetics Part A - December 28, 2017 Category: Genetics & Stem Cells Authors: Teresa Giugliano, Claudia Santoro, Annalaura Torella, Francesca Del Vecchio Blanco, Pia Bernardo, Vincenzo Nigro, Giulio Piluso Tags: CLINICAL REPORT Source Type: research

---
American Journal of Medical Genetics Part A,Volume 176, Issue 3, Page 722-726, March 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 28, 2017 Category: Genetics & Stem Cells Source Type: research

---
American Journal of Medical Genetics Part A,Volume 176, Issue 3, Page 743-745, March 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 28, 2017 Category: Genetics & Stem Cells Source Type: research

Phenotypic heterogeneity of POMT2 gene variants
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 28, 2017 Category: Genetics & Stem Cells Authors: Josef Finsterer Tags: CORRESPONDENCE Source Type: research

Genetic diagnosis of Down syndrome in an underserved community
It is a matter of course that in high‐income countries, infants born with features suggestive of Down syndrome (DS) are offered genetic testing for confirmation of a clinical diagnosis. Benefits of a definitive diagnosis include an end to the diagnostic odyssey, informed prognosis, opportunities for caregiver support, inclusion to social support networks, and more meaningful genetic counseling. The healthcare experience for families of children born with DS in low‐ and middle‐income nations is in stark contrast with such a level of care. Barriers to obtaining genetic diagnosis might include economic disparities, geog...
Source: American Journal of Medical Genetics Part A - December 26, 2017 Category: Genetics & Stem Cells Authors: Andrew K. Sobering, Joshua B. Stevens, Janice L. Smith, Beverly Nelson, Tyhiesia Donald, Sarah H. Elsea Tags: GENETIC DRIFT Source Type: research

Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies
In this report, four fetal or perinatal autopsy cases of arthrogryposis were studied by gross morphology, microscopic histopathologic examination, and whole genome sequencing of postmortem DNA. Two stillborn sibling fetuses with arthrogryposis, pterygia, and amyoplasia had compound heterozygous pathogenic variants in NEB. A neonate with a histopathologic diagnosis of nemaline myopathy had a heterozygous de novo pathogenic variant in ACTA1. Another stillborn infant with pterygia and arthrogryposis had a heterozygous de novo likely pathogenic variant in BICD2. These cases demonstrate the utility of whole genome sequencing as...
Source: American Journal of Medical Genetics Part A - December 23, 2017 Category: Genetics & Stem Cells Authors: Atif A. Ahmed, Priya Skaria, Nicole P. Safina, Isabelle Thiffault, Alex Kats, Eugenio Taboada, Sultan Habeebu, Carol Saunders Tags: ORIGINAL ARTICLE Source Type: research

Severe rhizomelic shortening in a child with a complex duplication/deletion rearrangement of chromosome X
Mesomelic and rhizo‐mesomelic dysplasias are a group of disorders characterized by abnormal shortening of the limbs. One of the most common causes of mesomelic shortening is the loss of the transcription factor SHOX. In this clinical report, we present a patient who in addition to mesomelic shortening has severe rhizomelic shortening and developmental delay. Karyotyping revealed a recombinant X chromosome in which the region distal to Xp22.33 (where SHOX is found) was replaced with material from Xq28. Included in the region distal to Xq28 is the gene MECP2 and this patient presents with features of MECP2 duplication synd...
Source: American Journal of Medical Genetics Part A - December 22, 2017 Category: Genetics & Stem Cells Authors: Ashish R. Deshwar, Lucie Dupuis, Carsten Bergmann, James Stavropoulos, Roberto Mendoza ‐Londono Tags: CLINICAL REPORT Source Type: research

The novel RAF1 mutation p.(Gly361Ala) located outside the kinase domain of the CR3 region in two patients with Noonan syndrome, including one with a rare brain tumor
We present two boys with Noonan syndrome and the identical de novo RAF1 missense variant c.1082G>C/p.(Gly361Ala) affecting the CR3, but located outside the kinase activation segment. The p.(Gly361Ala) mutation has been identified as a RAF1 allele conferring resistance to RAF inhibitors. This amino acid change favors a RAF1 conformation that allows for enhanced RAF dimerization and increased intrinsic kinase activity. Both patients with Noonan syndrome showed typical craniofacial dysmorphism, macrocephaly, and short stature. One individual developed HCM and was diagnosed with a disseminated oligodendroglial‐like leptom...
Source: American Journal of Medical Genetics Part A - December 22, 2017 Category: Genetics & Stem Cells Authors: Frederike L. Harms, Malik Alawi, David J. Amor, Tiong Y. Tan, Goran Cuturilo, Christina Lissewski, Julia Brinkmann, Denny Schanze, Kerstin Kutsche, Martin Zenker Tags: CLINICAL REPORT Source Type: research

Expanding the phenotype associated with biallelic WDR60 mutations: Siblings with retinal degeneration and polydactyly lacking other features of short rib thoracic dystrophies
Ciliopathies are disorders of the primary cilium that can affect almost all organs and that are characterized by pleiotropy and extensive intra‐ and interfamilial phenotypic variability. Accordingly, mutations in the same gene can cause different ciliopathy phenotypes of varying severity. WDR60 encodes a protein thought to play a role in the primary cilium's intraflagellar transport machinery. Mutations in this gene are a rare cause of Jeune asphyxiating thoracic dystrophy (JATD) and short‐rib polydactyly syndrome (SRPS). Here we report on a milder and distinct phenotype in a consanguineous Pakistani pedigree with two ...
Source: American Journal of Medical Genetics Part A - December 22, 2017 Category: Genetics & Stem Cells Authors: Naseebullah Kakar, Denise Horn, Eva Decker, Nadine Sowada, Christian Kubisch, Jamil Ahmad, Guntram Borck, Carsten Bergmann Tags: CLINICAL REPORT Source Type: research

Elsahy –Waters syndrome is caused by biallelic mutations in CDH11
Elsahy–Waters syndrome (EWS), also known as branchial–skeletal–genital syndrome, is a distinct dysmorphology syndrome characterized by facial asymmetry, broad forehead, marked hypertelorism with proptosis, short and broad nose, midface hypoplasia, intellectual disability, and hypospadias. We have recently published a homozygous potential loss of function variant in CDH11 in a boy with a striking resemblance to EWS. More recently, another homozygous truncating variant in CDH11 was reported in two siblings with suspected EWS. Here, we describe in detail the clinical phenotype of the original CDH11‐related...
Source: American Journal of Medical Genetics Part A - December 22, 2017 Category: Genetics & Stem Cells Authors: Frederike L. Harms, Sheela Nampoothiri, Shams Anazi, Dhanya Yesodharan, Malik Alawi, Kerstin Kutsche, Fowzan S. Alkuraya Tags: RAPID COMMUNICATION Source Type: research

Prader –Willi syndrome and early‐onset morbid obesity NIH rare disease consortium: A review of natural history study
We describe the National Institutes of Health rare disease consortium for Prader–Willi syndrome (PWS) developed to address concerns regarding medical care, diagnosis, growth and development, awareness, and natural history. PWS results from errors in genomic imprinting leading to loss of paternally expressed genes due to 15q11‐q13 deletion, maternal disomy 15 or imprinting defects. The 8 year study was conducted at four national sites on individuals with genetically confirmed PWS and early‐onset morbid obesity (EMO) with data accumulated to gain a better understanding of the natural history, cause and treatment of...
Source: American Journal of Medical Genetics Part A - December 22, 2017 Category: Genetics & Stem Cells Authors: Merlin G. Butler, Virginia Kimonis, Elisabeth Dykens, June A. Gold, Jennifer Miller, Roy Tamura, Daniel J. Driscoll Tags: ORIGINAL ARTICLE Source Type: research

A novel SAMD9 mutation causing MIRAGE syndrome: An expansion and review of phenotype, dysmorphology, and natural history
Germline gain‐of‐function variants in SAMD9 have been associated with a high risk of mortality and a newly recognized constellation of symptoms described by the acronym MIRAGE: Myelodysplasia, Infection, Restriction of growth, Adrenal insufficiency, Genital phenotypes, and Enteropathy. Here, we describe two additional patients currently living with the syndrome, including one patient with a novel de novo variant for which we provide functional data supporting its pathogenicity. We discuss features of dysmorphology, contrasting with previously described patients as well as drawing attention to additional clinical featur...
Source: American Journal of Medical Genetics Part A - December 21, 2017 Category: Genetics & Stem Cells Authors: Lauren Jeffries, Hirohito Shima, Weizhen Ji, David Panisello ‐Manterola, James McGrath, Lynne M. Bird, Monica Konstantino, Satoshi Narumi, Saquib Lakhani Tags: CLINICAL REPORT Source Type: research

Manifestation of recessive combined D ‐2‐, L‐2‐hydroxyglutaric aciduria in combination with 22q11.2 deletion syndrome
We report here for the first time a patient who manifested combined D‐2‐ and L‐2‐hydroxyglutaric aciduria as a result of a hemizygous mutation in SLC25A1 in combination with 22q11.2 deletion. The girl was diagnosed to have ACC shortly after birth and a deletion of 22q11.2 was identified by genetic analysis. Although the patient showed cardiac anomalies, which is one of the typical symptoms of 22q11.2 deletion syndrome, her rather severe phenotype and atypical face prompted us to search for additional pathogenic mutations. Three genes present in the deleted 22q11.2 region, SLC25A1, TUBA8, and SNAP29, which have been...
Source: American Journal of Medical Genetics Part A - December 19, 2017 Category: Genetics & Stem Cells Authors: Mariko Eguchi, Erina Ozaki, Toshifumi Yamauchi, Masaaki Ohta, Takashi Higaki, Kiyoshi Masuda, Issei Imoto, Eiichi Ishii, Minenori Eguchi ‐Ishimae Tags: ORIGINAL ARTICLE Source Type: research

The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome
This report expands the phenotypic spectrum for biallelic RNU4ATAC disorder causing variants and is the first to establish the genetic cause for Lowry Wood syndrome. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 19, 2017 Category: Genetics & Stem Cells Authors: Laura S. Farach, Mary E. Little, Angela L. Duker, Clare V. Logan, Andrew Jackson, Jaqueline T. Hecht, Michael Bober Tags: CLINICAL REPORT Source Type: research

Patient perspectives on the use of categories of conditions for decision making about genomic carrier screening results
As expanded genome‐scale carrier screening becomes increasingly prevalent, patients will face decisions about whether to receive results about a vast number of genetic conditions. Understanding patient preferences is important to meaningfully demonstrate the ethical goal of respect and support patient autonomy. We explore one possible way to elicit preferences by sorting conditions into categories, which may support patient decision making, but the extent to which categories are helpful is unknown. In the context of a randomized trial of genome sequencing for preconception carrier screening compared to usual care (single...
Source: American Journal of Medical Genetics Part A - December 18, 2017 Category: Genetics & Stem Cells Authors: Stephanie A. Kraft, Carmit K. McMullen, Kathryn M. Porter, Tia L. Kauffman, James V. Davis, Jennifer L. Schneider, Katrina A. B. Goddard, Benjamin S. Wilfond Tags: ORIGINAL ARTICLE Source Type: research

VACTERL phenotype with mosaic trisomy 5 and uniparental disomy 5
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 18, 2017 Category: Genetics & Stem Cells Authors: Samuel Hwang, Mary Katharine Rudd, Lisa Finch, Suzanne E. Peterson, Raj P. Kapur Tags: CORRESPONDENCE Source Type: research

Allometric considerations when assessing aortic aneurysms in Turner syndrome: Implications for activity recommendations and medical decision ‐making
In Turner syndrome, the potential to form thoracic aortic aneurysms requires routine patient monitoring. However, the short stature that typically occurs complicates the assessment of severity and risk because the relationship of body size to aortic dimensions is different in Turner syndrome compared to the general population. Three allometric formula have been proposed to adjust aortic dimensions, all employing body surface area: aortic size index, Turner syndrome‐specific Z‐scores, and Z‐scores based on a general pediatric and young adult population. In order to understand the differences between these formula we e...
Source: American Journal of Medical Genetics Part A - December 15, 2017 Category: Genetics & Stem Cells Authors: Holly Corbitt, Cheryl Maslen, Siddharth Prakash, Shaine A. Morris, Michael Silberbach Tags: ORIGINAL ARTICLE Source Type: research

Associations between laterality of orofacial clefts and medical and academic outcomes
Patients with oral clefts have an increased risk of other malformations, syndromes, and lower academic performance in school. Few studies have investigated if laterality of clefts is associated with medical and academic outcomes. Oral clefts have nonrandom laterality, with left‐sided clefts occurring approximately twice as often as right‐sided clefts. Using a retrospective study design, we examined potential associations of cleft attributes and outcomes in patients with cleft lip with or without cleft palate (CL/P) born in 2003–2010 who were treated at the Seattle Children's Craniofacial Center. The following var...
Source: American Journal of Medical Genetics Part A - December 12, 2017 Category: Genetics & Stem Cells Authors: Emily R. Gallagher, Babette Siebold, Brent R. Collett, Timothy C. Cox, Verena Aziz, Michael L. Cunningham 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 - December 12, 2017 Category: Genetics & Stem Cells Tags: the AJMG SEQUENCE: Decoding News and Trends for the Medical Genetics Community by Deborah Levenson Source Type: research

Exome sequencing helps diagnose infants in the ICU
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 12, 2017 Category: Genetics & Stem Cells Tags: the AJMG SEQUENCE: Decoding News and Trends for the Medical Genetics Community by Deborah Levenson Source Type: research

Testing scenario for intellectual disability, developmental delay, and autism challenged
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 12, 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 - December 12, 2017 Category: Genetics & Stem Cells Tags: ISSUE INFORMATION Source Type: research

Table of Contents, Volume 176A, Number 1, January 2018
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 12, 2017 Category: Genetics & Stem Cells Tags: ISSUE INFORMATION Source Type: research

Cover Image, Volume 176A, Number 1, January 2018
The cover image, by Satoru Ikenoue et al., is based on the Clinical Report Discordant fetal phenotype of hypophosphatasia in two siblings, DOI: 10.1002/ajmg.a.38531. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 12, 2017 Category: Genetics & Stem Cells Authors: Satoru Ikenoue, Kei Miyakoshi, Tomohiro Ishii, Yu Sato, Toshimitsu Otani, Yohei Akiba, Yoshifumi Kasuga, Daigo Ochiai, Tadashi Matsumoto, Yosuke Ichihashi, Yohei Matsuzaki, Kanako Tachikawa, Toshimi Michigami, Gen Nishimura, Kazushige Ikeda, Tomonobu Hase Tags: COVER IMAGE Source Type: research

Spontaneously regressing brain lesions in Smith –Lemli–Opitz syndrome
We present three individuals with SLOS and lesions in the basal ganglia or brainstem detected by MRI that were concerning for tumor formation. However, the individuals’ clinical and neurological course remained stable, and the lesions regressed after several years. These lesions have similarities to spongiotic changes observed in individuals with neurofibromatosis type 1 (NF1). Notably, impaired activity of small GTPases is present in both SLOS and NF1, perhaps giving mechanistic insight into the formation of these lesions. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 11, 2017 Category: Genetics & Stem Cells Authors: An N. Dang Do, Eva H. Baker, Katherine E. Warren, Simona E. Bianconi, Forbes D. Porter Tags: CLINICAL REPORT Source Type: research

Spontaneous intramural duodenal hematoma as the manifestation of Noonan syndrome
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 11, 2017 Category: Genetics & Stem Cells Authors: Kazuki Yamazawa, Yohei Yamada, Tatsuo Kuroda, Hideki Mutai, Tatsuo Matsunaga, Osamu Komiyama, Takao Takahashi Tags: RESEARCH LETTER Source Type: research

Novel compound heterozygous mutations in GPT2 linked to microcephaly, and intellectual developmental disability with or without spastic paraplegia
We here describe novel compound heterozygous missense variants, NM_133443:c.[400C>T] and NM_133443:[1435G>A], in the glutamic‐pyruvic transaminase 2 (GPT2) gene in a large consanguineous family with two affected siblings diagnosed with microcephaly intellectual disability and developmental delay (IDD). In addition to these clinical phenotypes, the male sibling has spastic paraplegia, and the female sibling has epilepsy. Their four extended family members have IDD and microcephaly. Both of these variants, c.400C>T (p.R134C) and c.1435G>A (p.V479M), reside in the pyridoxal phosphate‐dependent aminotransferase...
Source: American Journal of Medical Genetics Part A - December 11, 2017 Category: Genetics & Stem Cells Authors: Hande Kaymakcalan, Yanki Yarman, Nukte Goc, Fatih Toy, Cihan Meral, A. Gulhan Ercan ‐Sencicek, Murat Gunel Tags: CLINICAL REPORT Source Type: research

A novel truncating variant within exon 7 of KAT6B associated with features of both Say –Barber–Bieseker–Young–Simpson syndrome and genitopatellar syndrome: Further evidence of a continuum in the clinical spectrum of KAT6B‐related disorders
KAT6B sequence variants have been identified in both patients with the Say–Barber–Biesecker–Young–Simpson syndrome (SBBYSS) and in the genitopatellar syndrome (GPS). In SBBYSS, they were reported to affect mostly exons 16–18 of KAT6B, and the predicted mechanism of pathogenesis was haploinsufficiency or a partial loss of protein function. Truncating variants in KAT6B leading to GPS appear to cluster within the proximal portion of exon 18, associated with a dominant‐negative effect of the mutated protein, most likely. Although SBBYSS and GPS have been initially considered allelic disorders wi...
Source: American Journal of Medical Genetics Part A - December 11, 2017 Category: Genetics & Stem Cells Authors: Giuseppe Marangi, Marilena C. Di Giacomo, Serena Lattante, Daniela Orteschi, Sara Patrizi, Paolo N. Doronzio, Francesco N. Riviello, Alessandro Vaisfeld, Silvia Frangella, Marcella Zollino Tags: CLINICAL REPORT Source Type: research

Mixoploidy combined with aneuploidy in a 13 year ‐old patient with severe multiple congenital abnormalities and intellectual disability
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 11, 2017 Category: Genetics & Stem Cells Authors: Laura J. C. M. van Zutven, Grazia M. S. Mancini, Karen G. C. B. Bindels −de Heus, Erica L. T. van den Akker, Lorette O. M. Hulsman, Marjan Smit, H. Berna Beverloo Tags: RESEARCH LETTER Source Type: research

A novel homozygous SLC25A1 mutation with impaired mitochondrial complex V: Possible phenotypic expansion
SLC25A1 mutations are associated with combined D,L‐2‐hydroxyglutaric aciduria (DL‐ 2HGA; OMIM #615182), characterized by muscular hypotonia, severe neurodevelopmental dysfunction and intractable seizures. SLC25A1 encodes the mitochondrial citrate carrier (CIC), which mediates efflux of the mitochondrial tricarboxylic acid (TCA) cycle intermediates citrate and isocitrate in exchange for cytosolic malate. Only a single family with an SLC25A1 mutation has been described in which mitochondrial respiratory chain dysfunction was documented, specifically in complex IV. Five infants of two consanguineous Bedouin families of ...
Source: American Journal of Medical Genetics Part A - December 11, 2017 Category: Genetics & Stem Cells Authors: Idan Cohen, Orna Staretz ‐Chacham, Ohad Wormser, Yonatan Perez, Ann Saada, Rotem Kadir, Ohad S. Birk Tags: ORIGINAL ARTICLE Source Type: research

Small supernumerary marker chromosome 15 and a ring chromosome 15 associated with a 15q26.3 deletion excluding the IGF1R gene
We present a child with epilepsy, cardiac symptoms, severely delayed mental and growth development, behavioral disturbances and characteristic dysmorphic features showing a ring chromosome 15 and a small supernumerary marker chromosome. Array CGH detected a 1 Mb deletion of 15q26.3 in a ring chromosome 15 and a 2.6 Mb copy number gain of 15q11.2 corresponding to a small supernumerary marker chromosome involving proximal 15q. Our findings add to previously published results of 15q11q13 duplications and 15q26 terminal deletions. Based on our study we can support the previous reported limited information about t...
Source: American Journal of Medical Genetics Part A - December 11, 2017 Category: Genetics & Stem Cells Authors: Andr ás Szabó, Márta Czakó, Kinga Hadzsiev, Balázs Duga, Zsolt Bánfai, Katalin Komlósi, Béla Melegh Tags: CLINICAL REPORT Source Type: research

Therapy development in Huntington disease: From current strategies to emerging opportunities
American Journal of Medical Genetics Part A,Volume 176, Issue 4, Page 842-861, April 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 8, 2017 Category: Genetics & Stem Cells Source Type: research

---
American Journal of Medical Genetics Part A, Ahead of Print. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 8, 2017 Category: Genetics & Stem Cells Source Type: research

Intrafamilial variability in the clinical manifestations of mucopolysaccharidosis type II: Data from the Hunter Outcome Survey (HOS)
Several cases of phenotypic variability among family members with mucopolysaccharidosis type II (MPS II) have been reported, but the data are limited. Data from patients enrolled in the Hunter Outcome Survey (HOS) were used to investigate intrafamilial variability in male siblings with MPS II. As of July 2015, data were available for 78 patients aged ≥5 years at last visit who had at least one affected sibling (39 sibling pairs). These patients were followed prospectively (i.e., they were alive at enrollment in HOS). The median age at the onset of signs and symptoms was the same for the elder and younger brothers (2.0 y...
Source: American Journal of Medical Genetics Part A - December 6, 2017 Category: Genetics & Stem Cells Authors: Can Ficicioglu, Roberto Giugliani, Paul Harmatz, Nancy J. Mendelsohn, Virginie Jego, Rossella Parini Tags: ORIGINAL ARTICLE Source Type: research

Auditory evoked potentials in children and adolescents with Down syndrome
Down syndrome, or trisomy 21, is the most common genetic alteration in humans. The syndrome presents with several features, including hearing loss and changes in the central nervous system, which may affect language development in children and lead to school difficulties. The present study aimed to investigate group differences in the central auditory system by long‐latency auditory evoked potentials and cognitive potential. An assessment of 23 children and adolescents with Down syndrome was performed, and a control group composed of 43 children and adolescents without genetic and/or neurological changes was used for com...
Source: American Journal of Medical Genetics Part A - December 6, 2017 Category: Genetics & Stem Cells Authors: Let ícia Gregory, Rafael F. M. Rosa, Paulo R. G. Zen, Pricila Sleifer Tags: ORIGINAL ARTICLE Source Type: research

A child with Myhre syndrome presenting with corectopia and tetralogy of Fallot
We report a 2‐year‐old girl diagnosed with Myhre syndrome by whole exome sequencing (WES) that revealed the recurrent p.Ile500Val mutation in the SMAD4 gene. Our patient presented with growth deficiency, dysmorphic features, tetralogy of Fallot, and corectopia (also known as ectopia pupillae). The girl we described is the youngest patient with Myhre syndrome. Moreover, corectopia and tetralogy of Fallot have not been previously reported in this disorder. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 1, 2017 Category: Genetics & Stem Cells Authors: Marianna Alagia, Gerarda Cappuccio, Michele Pinelli, Annalaura Torella, Raffaella Brunetti ‐Pierri, Francesca Simonelli, Giuseppe Limongelli, Guido Oppido, Vincenzo Nigro, Nicola Brunetti‐Pierri, Tags: CLINICAL REPORT Source Type: research

Autopsy findings in EPG5 ‐related Vici syndrome with antenatal onset: Additional report of Focal cortical microdysgenesis in a second trimester fetus
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - December 1, 2017 Category: Genetics & Stem Cells Authors: Shagun Aggarwal, Ashwani Tandon, Aneek Das Bhowmik, Ashwin Dalal Tags: LETTER TO THE EDITOR Source Type: research