title: Mutations in the NEB gene cause fetal akinesia/arthrogryposis multiplex congenita.
abstract: OBJECTIVE
  We studied a series of patients with fetal akinesia deformation sequence (FADS)/arthrogryposis multiplex congenita (AMC), with nemaline bodies on muscle specimens, which revealed mutations in the NEB gene.
  
  
  METHODS
  We pathologically assessed seven cases from three families, who presented with AMC/FADS. Targeted genetic analysis for Ashkenazi Jewish mutation (in relevant patients) was followed by next-generation sequencing and multiplex ligation-dependent probe amplification.
  
  
  RESULTS
  All cases were detected on prenatal ultrasound. Characteristic nemaline bodies on muscle specimens were demonstrated in at least one case in each of the nuclear families. In the Ashkenazi Jewish family, the known founder mutation was compounded by one recurrent novel splice site. The other two families were of Chinese and Korean origins, and only one pathogenic heterozygous mutation was detected in each.
  
  
  CONCLUSIONS
  Nemaline myopathy due to NEB mutation(s) leads to FADS/AMC. Currently, mutated NEB is under-recognized as a cause for AMC/FADS. Our study attempts to raise recognition of this gene as a cause, suggesting the NEB gene should be included in genetic panels used for FADS/AMC cases and be fully covered when EXOME sequencing is utilized. A heterozygous mutation may suggest either compounding undetected one or digenic interaction that requires further genetic analyses. © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Genetic Institute, Assaf Harofeh Medical Center, Zerifin, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|Department of Obstetrics and Gynecology Ward, Ultrasound Unit, Assaf Harofeh Medical Center, Zerifin, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Feingold-Zadok
authors.affiliation: Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.affiliation: Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Chong
authors.affiliation: Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marie
authors.initials: M
authors.lastname: Injeyan
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Shannon
authors.affiliation: Genetic Institute, Assaf Harofeh Medical Center, Zerifin, Israel.
authors.forename: Daphne
authors.initials: D
authors.lastname: Chapmann
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|Department of Obstetrics and Gynecology Ward, Ultrasound Unit, Assaf Harofeh Medical Center, Zerifin, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Maymon
authors.affiliation: Bioinformatic Division, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Pillar
authors.affiliation: Genetic Institute, Assaf Harofeh Medical Center, Zerifin, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Reish
mesh_terms: D000025:Abortion, Eugenic; D001176:Arthrogryposis / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy
chemical_list: D009124:Muscle Proteins; C035620:nebulin