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A recognizable type of syndromic short stature with arthrogryposis caused by bi‐allelic SEMA3A loss‐of‐function variants
Author(s) -
Baumann M.,
SteichenGersdorf E.,
Krabichler B.,
Müller T.,
Janecke A.R.
Publication year - 2017
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12967
Subject(s) - camptodactyly , sema3a , biology , short stature , exome sequencing , craniosynostosis , loss function , brachydactyly , phenotype , genetics , syndactyly , micropenis , allele , arthrogryposis , semaphorin , endocrinology , gene , receptor , hypospadias
The semaphorins constitute a large family of secreted and membrane‐associated proteins that regulate many developmental processes, including neural circuit assembly, bone formation and angiogenesis. Recently, bi‐allelic loss‐of‐function variants in SEMA3A (semaphorin 3A ) were identified in a single patient with a particular pattern of multiple congenital anomalies ( MCA ). Using homozygosity mapping combined with exome sequencing, we identified a homozygous SEMA3A variant causing a premature stop codon in an 8 year old boy with the same pattern of MCA . The phenotype of these patients is characterized by postnatal short stature, skeletal anomalies of the thorax, a minor congenital heart or vascular defect, camptodactyly, micropenis, and variable additional anomalies. Motor development is delayed in both patients, and intellectual development is delayed in one patient. Our observation of a second case supports the notion that bi‐allelic mutations in SEMA3A cause an autosomal recessive type of syndromic short stature.