title: A recognizable type of syndromic short stature with arthrogryposis caused by bi-allelic SEMA3A loss-of-function variants.
abstract: 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.
authors.affiliation: Department of Paediatrics I, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Department of Paediatrics I, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Steichen-Gersdorf
authors.affiliation: Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Krabichler
authors.affiliation: Department of Paediatrics I, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Müller
authors.affiliation: Department of Paediatrics I, Medical University of Innsbruck, Innsbruck, Austria.|Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: A R
authors.identifier: http://orcid.org/0000-0001-7155-0315
authors.initials: AR
authors.lastname: Janecke
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D000483:Alleles; D001176:Arthrogryposis / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004392:Dwarfism / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D006720:Homozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D040121:Semaphorin-3A / Q000235:genetics*
chemical_list: C108639:SEMA3A protein, human; D040121:Semaphorin-3A
keywords: 
  MCA syndrome; 
  SEMA3A
  ; camptodactyly; developmental; rib dysplasia; scapula dysplasia; semaphorin; short stature; thorax anomaly