{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:41:45Z","timestamp":1790329305399,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,10,3]],"date-time":"2013-10-03T00:00:00Z","timestamp":1380758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Chromosomal microarray testing is commonly used to identify disease causing de novo copy number variants in patients with developmental delay and multiple congenital anomalies. In such a patient we now observed an 150\u2009kb deletion on chromosome 7q21.11 affecting the first exon of the axon guidance molecule gene <jats:italic>SEMA3A<\/jats:italic> (sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3A). This deletion was inherited from the healthy father, but considering the function of SEMA3A and phenotypic similarity to the knock\u2010out mice, we still assumed a pathogenic relevance and tested for a recessive second defect. Sequencing of <jats:italic>SEMA3A<\/jats:italic> in the patient indeed revealed the de novo in\u2010frame mutation p.Phe316_Lys317delinsThrSerSerAsnGlu. Cloning of the mutated allele in combination with two informative SNPs confirmed compound heterozygosity in the patient. While the altered protein structure was predicted to be benign, aberrant splicing resulting in a premature stop codon was proven by RT\u2010PCR to occur in about half of the transcripts from this allele. Expression profiling in human fetal and adult cDNA panels, confirmed a high expression of <jats:italic>SEMA3A<\/jats:italic> in all brain regions as well as in adult and fetal heart and fetal skeletal muscle. Normal intellectual development in the patient was surprising but may be explained by the remaining 20% of <jats:italic>SEMA3A<\/jats:italic> expression level demonstrated by quantitative RT\u2010PCR. We therefore report a novel autosomal recessive syndrome characterized by postnatal short stature with relative macrocephaly, camptodactyly, septal heart defect and several minor anomalies caused by biallelic mutations in <jats:italic>SEMA3A<\/jats:italic>. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36250","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T02:38:17Z","timestamp":1381545497000},"page":"2880-2889","source":"Crossref","is-referenced-by-count":12,"title":["Biallelic <i>SEMA3A<\/i> defects cause a novel type of syndromic short stature"],"prefix":"10.1002","volume":"161","author":[{"given":"Kristin","family":"Hofmann","sequence":"first","affiliation":[{"name":"Institute of Human Genetics Friedrich\u2010Alexander University Erlangen\u2010Nuremberg Erlangen 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