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Mutations in the NEB gene cause fetal akinesia/arthrogryposis multiplex congenita
Author(s) -
FeingoldZadok Michal,
Chitayat David,
Chong Karen,
Injeyan Marie,
Shan Patrick,
Chapmann Daphne,
Maymon Ron,
Pillar Nir,
Reish Orit
Publication year - 2017
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.4977
Subject(s) - nemaline myopathy , arthrogryposis multiplex congenita , arthrogryposis , multiplex ligation dependent probe amplification , mutation , genetics , prenatal diagnosis , biology , congenital myopathy , exome sequencing , gene mutation , compound heterozygosity , gene , medicine , fetus , muscle biopsy , pathology , exon , biopsy , pregnancy
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. Method 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.