---
American Journal of Medical Genetics Part A,Volume 176, Issue 3, Page 505-508, March 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 15, 2018 Category: Genetics & Stem Cells Source Type: research

Gratitude, protective buffering, and cognitive dissonance: How families respond to pediatric whole exome sequencing in the absence of actionable results
This study investigated how families understand findings and adjust their perspectives on CGES. As part of NIH's Clinical Sequencing Exploratory Research Consortium, children were recruited from clinics at the Children's Hospital of Pennsylvania (CHOP) and offered exome sequencing. Primary pathogenic and possibly pathogenic, and some secondary findings were returned. Investigators digitally recorded results disclosure sessions and conducted 3‐month follow up interviews with 10 adolescents and a parent. An interdisciplinary team coded all transcripts. Participants were initially disappointed with findings, yet reactions e...
Source: American Journal of Medical Genetics Part A - February 15, 2018 Category: Genetics & Stem Cells Authors: Allison Werner ‐Lin, Lori Zaspel, Mae Carlson, Rebecca Mueller, Sarah A. Walser, Ria Desai, Barbara A. Bernhardt 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 - February 15, 2018 Category: Genetics & Stem Cells Tags: the AJMG SEQUENCE: Decoding News and Trends for the Medical Genetics Community by Bryn Nelson, PhD Source Type: research

Making a (cautious) case for expanding reproductive genetic carrier screens
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 15, 2018 Category: Genetics & Stem Cells Tags: the AJMG SEQUENCE: Decoding News and Trends for the Medical Genetics Community by Bryn Nelson, PhD Source Type: research

Publication schedule for 2018
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 15, 2018 Category: Genetics & Stem Cells Tags: ISSUE INFORMATION Source Type: research

Table of Contents, Volume 176A, Number 3, March 2018
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 15, 2018 Category: Genetics & Stem Cells Tags: ISSUE INFORMATION Source Type: research

Cover Image, Volume 176A, Number 3, March 2018
The cover image, by Kei Tamai et al., is based on the Clinical Report Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient with non‐lethal form of Raine syndrome, DOI: 10.1002/ajmg.a.38598. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 15, 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: COVER IMAGE Source Type: research

Three siblings with Prader –Willi syndrome caused by imprinting center microdeletions and review
American Journal of Medical Genetics Part A,Volume 176, Issue 4, Page 886-895, April 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 13, 2018 Category: Genetics & Stem Cells Source Type: research

A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis
American Journal of Medical Genetics Part A,Volume 176, Issue 4, Page 1015-1022, April 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 13, 2018 Category: Genetics & Stem Cells Source Type: research

Natural history and genotype ‐phenotype correlations in 72 individuals with SATB2‐associated syndrome
American Journal of Medical Genetics Part A,Volume 176, Issue 4, Page 925-935, April 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 13, 2018 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 - February 13, 2018 Category: Genetics & Stem Cells Source Type: research

Natural history and genotype ‐phenotype correlations in 72 individuals with SATB2‐associated syndrome
SATB2‐associated syndrome (SAS) is an autosomal dominant disorder characterized by significant neurodevelopmental disabilities with limited to absent speech, behavioral issues, and craniofacial anomalies. Previous studies have largely been restricted to case reports and small series without in‐depth phenotypic characterization or genotype‐phenotype correlations. Seventy two study participants were identified as part of the SAS clinical registry. Individuals with a molecularly confirmed diagnosis of SAS were referred after clinical diagnostic testing. In this series we present the most comprehensive phenotypic and gen...
Source: American Journal of Medical Genetics Part A - February 13, 2018 Category: Genetics & Stem Cells Authors: Yuri A. Zarate, Constance L. Smith ‐Hicks, Carol Greene, Mary‐Alice Abbott, Victoria M. Siu, Amy R. U. L. Calhoun, Arti Pandya, Chumei Li, Elizabeth A. Sellars, Julie Kaylor, Katherine Bosanko, Louisa Kalsner, Alice Basinger, Anne M. Slavotinek, Hazel Tags: ORIGINAL ARTICLE Source Type: research

A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis
We report the clinical and genetic impact of a rare homozygous ANTXR1 variant (c.1312C>T), identified by whole exome sequencing (WES), in a consanguineous Turkish family with TA. Mutations in ANTXR1 have been associated with GAPO (growth retardation, alopecia, pseudoanodontia, and optic atrophy) syndrome and infantile hemangioma, however no clinical characteristics associated with these conditions were observed in our study family. We detected the expression of Antxr1 in oral and dental tissues of developing mouse embryos, further supporting a role for this gene in tooth development. Our findings implicate ANTXR1 as a c...
Source: American Journal of Medical Genetics Part A - February 13, 2018 Category: Genetics & Stem Cells Authors: Nuriye Dinckan, Renqian Du, Zeynep C. Akdemir, Yavuz Bayram, Shalini N. Jhangiani, Harsha Doddapaneni, Jianhong Hu, Donna M. Muzny, Yeliz Guven, Oya Aktoren, Hulya Kayserili, Eric Boerwinkle, Richard A. Gibbs, Jennifer E. Posey, James R. Lupski, Zehra O. Tags: CLINICAL REPORT Source Type: research

A novel homozygous AP4B1 mutation in two brothers with AP ‐4 deficiency syndrome and ocular anomalies
American Journal of Medical Genetics Part A,Volume 176, Issue 4, Page 985-991, April 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 12, 2018 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 - February 12, 2018 Category: Genetics & Stem Cells Source Type: research

Non ‐syndromic bilateral ulnar aplasia with humero‐radial synostosis and oligo‐ectro‐dactyly
American Journal of Medical Genetics Part A, EarlyView. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 10, 2018 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 - February 10, 2018 Category: Genetics & Stem Cells Source Type: research

The art and science of choosing efficacy endpoints for rare disease clinical trials
American Journal of Medical Genetics Part A,Volume 176, Issue 4, Page 759-772, April 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 9, 2018 Category: Genetics & Stem Cells Source Type: research

Two de novo novel mutations in one SHANK3 allele in a patient with autism and moderate intellectual disability
American Journal of Medical Genetics Part A,Volume 176, Issue 4, Page 973-979, April 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 9, 2018 Category: Genetics & Stem Cells Source Type: research

International investigation of neurocognitive and behavioral phenotype in 47,XXY (Klinefelter syndrome): Predicting individual differences
American Journal of Medical Genetics Part A,Volume 176, Issue 4, Page 877-885, April 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 9, 2018 Category: Genetics & Stem Cells Source Type: research

ICD ‐10 impact on ascertainment and accuracy of oral cleft cases as recorded by the Brazilian national live birth information system
American Journal of Medical Genetics Part A,Volume 176, Issue 4, Page 907-914, April 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 9, 2018 Category: Genetics & Stem Cells Source Type: research

Leg length, sitting height, and body proportions references for achondroplasia: New tools for monitoring growth
American Journal of Medical Genetics Part A,Volume 176, Issue 4, Page 896-906, April 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 9, 2018 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 - February 9, 2018 Category: Genetics & Stem Cells Source Type: research

International investigation of neurocognitive and behavioral phenotype in 47,XXY (Klinefelter syndrome): Predicting individual differences
This study lays additional features to the foundation for an algorithm linking external variables to outcome on various neurodevelopmental measures. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 9, 2018 Category: Genetics & Stem Cells Authors: Carole Samango ‐Sprouse, Emily Stapleton, Selena Chea, Patrick Lawson, Teresa Sadeghin, Chris Cappello, Leo de Sonneville, Sophie van Rijn Tags: ORIGINAL ARTICLE Source Type: research

Two de novo novel mutations in one SHANK3 allele in a patient with autism and moderate intellectual disability
SHANK3 encodes for a scaffolding protein that links neurotransmitter receptors to the cytoskeleton and is enriched in postsynaptic densities of excitatory synapses. Deletions or mutations in one copy of the SHANK3 gene cause Phelan‐McDermid syndrome, also called 22q13.3 deletion syndrome, a neurodevelopmental disorder with common features including global developmental delay, absent to severely impaired language, autistic behavior, and minor dysmorphic features. By whole exome sequencing, we identified two de novo novel variants including one frameshift pathogenic variant and one missense variant of unknown significance ...
Source: American Journal of Medical Genetics Part A - February 9, 2018 Category: Genetics & Stem Cells Authors: Wenmiao Zhu, Jianli Li, Stella Chen, Jinglan Zhang, Francesco Vetrini, Alicia Braxton, Christine M. Eng, Yaping Yang, Fan Xia, Kory L. Keller, Leila Okinaka ‐Hu, Chung Lee, J. Lloyd Holder, Weimin Bi Tags: CLINICAL REPORT Source Type: research

The art and science of choosing efficacy endpoints for rare disease clinical trials
An important challenge in rare disease clinical trials is to demonstrate a clinically meaningful and statistically significant response to treatment. Selecting the most appropriate and sensitive efficacy endpoints for a treatment trial is part art and part science. The types of endpoints should align with the stage of development (e.g., proof of concept vs. confirmation of clinical efficacy). The patient characteristics and disease stage should reflect the treatment goal of improving disease manifestations or preventing disease progression. For rare diseases, regulatory approval requires demonstration of clinical benefit, ...
Source: American Journal of Medical Genetics Part A - February 9, 2018 Category: Genetics & Stem Cells Authors: Gerald F. Cox Tags: RESEARCH REVIEW Source Type: research

Leg length, sitting height, and body proportions references for achondroplasia: New tools for monitoring growth
We report leg length, sitting height, and body proportion curves for achondroplasia. Seven centile format of sitting height, leg length, sitting height/leg length ratio, sitting height/height ratio, and head circumference/height ratio were estimated by the LMS method. The Q‐test was applied to assess the goodness of fit. For comparison, centiles of sitting height and leg length were graphed using Argentine national growth references for achondroplasia and non‐achondroplasia populations. The sample consisted of 342 children with achondroplasia (171 males, 171 females) aged 0–18 years. The median (interquartile ran...
Source: American Journal of Medical Genetics Part A - February 9, 2018 Category: Genetics & Stem Cells Authors: Mariana del Pino, Rosario Ramos Mej ía, Virginia Fano Tags: ORIGINAL ARTICLE Source Type: research

---
American Journal of Medical Genetics Part A,Volume 176, Issue 3, Page 618-637, March 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 5, 2018 Category: Genetics & Stem Cells Source Type: research

---
American Journal of Medical Genetics Part A,Volume 176, Issue 3, Page 609-617, March 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 5, 2018 Category: Genetics & Stem Cells Source Type: research

A parent ‐of‐origin analysis of paternal genetic variants and increased risk of conotruncal heart defects
The association between conotruncal heart defects (CTHDs) and maternal genetic and environmental exposures is well studied. However, little is known about paternal genetic or environmental exposures and risk of CTHDs. We assessed the effect of paternal genetic variants in the folate, homocysteine, and transsulfuration pathways on risk of CTHDs in offspring. We utilized National Birth Defects Prevention Study data to conduct a family‐based case only study using 616 live‐born infants with CTHDs, born October 1997—August 2008. Maternal, paternal and infant DNA was genotyped using an Illumina® Golden Gate custom ...
Source: American Journal of Medical Genetics Part A - February 5, 2018 Category: Genetics & Stem Cells Authors: Wendy N. Nembhard, Xinyu Tang, Jingyun Li, Stewart L. MacLeod, Joseph Levy, Gerald B. Schaefer, Charlotte A. Hobbs, Tags: ORIGINAL ARTICLE Source Type: research

---
American Journal of Medical Genetics Part A,Volume 176, Issue 3, Page 733-738, March 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 2, 2018 Category: Genetics & Stem Cells Source Type: research

Incidence, puberty, and fertility in 45,X/47,XXX mosaicism: Report of a patient and a literature review
American Journal of Medical Genetics Part A,Volume 176, Issue 4, Page 1029-1029, April 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 1, 2018 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 - February 1, 2018 Category: Genetics & Stem Cells Source Type: research

---
American Journal of Medical Genetics Part A,Volume 176, Issue 3, Page 515-550, March 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 1, 2018 Category: Genetics & Stem Cells Source Type: research

---
American Journal of Medical Genetics Part A,Volume 176, Issue 3, Page 692-698, March 2018. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 1, 2018 Category: Genetics & Stem Cells Source Type: research

Three siblings with Prader –Willi syndrome caused by imprinting center microdeletions and review
Prader–Willi syndrome (PWS) is a complex genetic imprinting disorder characterized by childhood obesity, short stature, hypogonadism/hypogenitalism, hypotonia, cognitive impairment, and behavioral problems. Usually PWS occurs sporadically due to the loss of paternally expressed genes on chromosome 15 with the majority of individuals having the 15q11‐q13 region deleted. Examples of familial PWS have been reported but rarely. To date 13 families have been reported with more than one child with PWS and without a 15q11‐q13 deletion secondary to a chromosome 15 translocation, inversion, or uniparental maternal disomy ...
Source: American Journal of Medical Genetics Part A - February 1, 2018 Category: Genetics & Stem Cells Authors: Samantha N. Hartin, Waheeda A. Hossain, Nicolette Weisensel, Merlin G. Butler Tags: ORIGINAL ARTICLE Source Type: research

A novel homozygous AP4B1 mutation in two brothers with AP ‐4 deficiency syndrome and ocular anomalies
Adaptor protein complex‐4 (AP‐4) is a heterotetrameric protein complex which plays a key role in vesicle trafficking in neurons. Mutations in genes affecting different subunits of AP‐4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been recently associated with an autosomal recessive phenotype, consisting of spastic tetraplegia, and intellectual disability (ID). The overlapping clinical picture among individuals carrying mutations in any of these genes has prompted the terms “AP‐4 deficiency syndrome” for this clinically recognizable phenotype. Using whole‐exome sequencing, we identified a novel homo...
Source: American Journal of Medical Genetics Part A - February 1, 2018 Category: Genetics & Stem Cells Authors: Andrea Accogli, Fadi F. Hamdan, Chantal Poulin, Christina Nassif, Guy A. Rouleau, Jacques L. Michaud, Myriam Srour Tags: CLINICAL REPORT Source Type: research

Non ‐syndromic bilateral ulnar aplasia with humero‐radial synostosis and oligo‐ectro‐dactyly
Congenital anomalies of the upper limbs are rare and etiologically heterogeneous. Herein, we report a male infant with non‐syndromic bilateral Type Vb ulnar longitudinal dysplasia with radiohumeral synostosis (apparent humeral bifurcation), and bilateral oligo‐ectro‐syndactyly who was born following an uncomplicated pregnancy, with no maternal use of prescription or illicit medication. Array CGH (60,000 probes) and chromosomal breakage analysis (DEB) were normal. Similar appearances have been reported in children exposed to thalidomide or cocaine, but sporadic patients have also been reported without a prior history ...
Source: American Journal of Medical Genetics Part A - February 1, 2018 Category: Genetics & Stem Cells Authors: Terri P. McVeigh, Jonathan A. Soye, Emma Gordon, Sally A. Lynch Tags: CLINICAL REPORT Source Type: research

ICD ‐10 impact on ascertainment and accuracy of oral cleft cases as recorded by the Brazilian national live birth information system
We compared Brazilian oral cleft (OC) frequencies between the population‐based Brazilian System of Live Birth (SINASC) and the hospital‐based Latin American Collaborative Study of Congenital Malformations (ECLAMC), trying to understand the paucity of cleft of lip and palate (CLP) in the first system. SINASC uses the International Classification of Disease version 10 (ICD‐10) for congenital defects coding, ECLAMC uses ICD‐8 with modifications. In SINASC, the CLP frequency was 1.7 per 10,000 (95% confidence limits 1.7–1.8), cleft lip (CL) 1.6 (1.5–1.7), and cleft palate (CP) 2.0 (1.9–2.1). In ECLAMC...
Source: American Journal of Medical Genetics Part A - February 1, 2018 Category: Genetics & Stem Cells Authors: L. R. Nascimento, Eduardo E. Castilla, M. R. Dutra, I êda M. Orioli Tags: ORIGINAL ARTICLE Source Type: research

History and highlights of the teratological collection in the Museum Anatomicum of Leiden University, The Netherlands
The anatomical collection of the Anatomical Museum of Leiden University Medical Center (historically referred to as Museum Anatomicum Academiae Lugduno‐Batavae) houses and maintains more than 13,000 unique anatomical, pathological and zoological specimens, and include the oldest teratological specimens of The Netherlands. Throughout four centuries hundreds of teratological specimens were acquired by more than a dozen collectors. Due to the rich history of this vast collection, teratological specimens can be investigated in a unique retrospective sight going back almost four centuries. The entire 19th century collection w...
Source: American Journal of Medical Genetics Part A - February 1, 2018 Category: Genetics & Stem Cells Authors: Lucas L. Boer, Peter L. J. Boek, Andries J. van Dam, Roelof ‐Jan Oostra Tags: ORIGINAL ARTICLE Source Type: research

CHILD syndrome: A modified pathogenesis ‐targeted therapeutic approach
Congenital Hemidysplasia with Ichthyosiform nevus and Limb Defects (CHILD syndrome) is a rare X‐linked dominant genodermatosis caused by mutations in the NAD(P) dependent steroid dehydrogenase‐like protein gene. Its defect leads to accumulation of toxic metabolic intermediates upstream from the pathway block and to the deficiency of bulk cholesterol, probably leading to altered keratinocyte membrane function, resulting in the phenotype seen in CHILD syndrome. Symptomatic treatment using emollients and retinoids to reduce scaling has long been used until recently, whereby new therapeutic means based on the pathogenesis...
Source: American Journal of Medical Genetics Part A - February 1, 2018 Category: Genetics & Stem Cells Authors: Christina Bergqvist, Bilal Abdallah, Divina ‐Justina Hasbani, Ossama Abbas, Abdul Ghani Kibbi, Lamiaa Hamie, Mazen Kurban, Nelly Rubeiz Tags: CLINICAL REPORT Source Type: research

Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant
Mitochondrial NAD kinase deficiency (NADK2D, OMIM #615787) is a rare autosomal recessive disorder of NADPH biosynthesis that can cause hyperlysinemia and dienoyl‐CoA reductase deficiency (DECRD, OMIM #616034). NADK2 deficiency has been reported in only three unrelated patients. Two had severe, unremitting disease; one died at 4 months and the other at 5 years of age. The third was a 10 year old female with CNS anomalies, ataxia, and incoordination. In two cases mutations in NADK2 have been demonstrated. Here, we report the fourth known case, a 15 year old female with normal intelligence and a mild clinical and biochemica...
Source: American Journal of Medical Genetics Part A - February 1, 2018 Category: Genetics & Stem Cells Authors: Daniel J. Pomerantz, Sacha Ferdinandusse, Joy Cogan, David N. Cooper, Tyler Reimschisel, Amy Robertson, Anna Bican, Tracy McGregor, Jackie Gauthier, David S. Millington, Jaime L. W. Andrae, Michael R. Tschannen, Daniel C. Helbling, Wendy M. Demos, Simone Tags: CLINICAL REPORT Source Type: research

Incidence, puberty, and fertility in 45,X/47,XXX mosaicism: Report of a patient and a literature review
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 1, 2018 Category: Genetics & Stem Cells Authors: Richard J. Martin, Geoff Smith, James Hughes, Patrick J. Morrison Tags: CORRESPONDENCE Source Type: research

Early history of the different forms of neurofibromatosis from ancient Egypt to the British Empire and beyond: First descriptions, medical curiosities, misconceptions, landmarks, and the persons behind the syndromes
The earliest examples of neurofibromatosis (in this case type 1, NF1) can be traced in the Ebers Papyrus (Ancient Egypt, 1.500 B.C.), in a Hellenistic statuette (Smyrna, 323 B.C.), in the coinage of the Parthians kings (247 B.C.) and in some 13th century monks' drawings. These earlier examples are somewhat less well defined as compared to the most recent better defined reports credited as having NF1 including an Inca child mummy (1480—1650 AD), Ulisse Aldrovandi's homuncio (“Monstrorum Historia”, 1592 A.D.) with mosaic NF1 or the illustrations seen in the 18th century “Buffon's Histoire Naturelle&rd...
Source: American Journal of Medical Genetics Part A - February 1, 2018 Category: Genetics & Stem Cells Authors: Martino Ruggieri, Andrea D. Pratic ò, Rosario Caltabiano, Agata Polizzi Tags: RESEARCH REVIEW Source Type: research