Biallelic SEMA3A defects cause a novel type of syndromic short stature

Beitrag in einer Fachzeitschrift

Details zur Publikation

Autorinnen und Autoren: Hofmann K, Zweier M, Sticht H, Zweier C, Wittmann W, Hoyer J, Uebe S, Van Haeringen A, Thiel C, Ekici AB, Reis A, Rauch A
Zeitschrift: American Journal of Medical Genetics Part A
Verlag: Wiley-Blackwell
Jahr der Veröffentlichung: 2013
Band: 161A
Heftnummer: 11
Seitenbereich: 2880-9
ISSN: 1552-4825


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 kb deletion on chromosome 7q21.11 affecting the first exon of the axon guidance molecule gene SEMA3A (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-out mice, we still assumed a pathogenic relevance and tested for a recessive second defect. Sequencing of SEMA3A in the patient indeed revealed the de novo in-frame 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-PCR 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 SEMA3A 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 SEMA3A expression level demonstrated by quantitative RT-PCR. 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 SEMA3A.

FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Hofmann, Kristin
Lehrstuhl für Humangenetik
Sticht, Heinrich Prof. Dr.
Professur für Bioinformatik
Thiel, Christian PD Dr.
Medizinische Fakultät
Uebe, Steffen Dr. rer. nat.
Humangenetisches Institut
Zweier, Markus
Lehrstuhl für Humangenetik
Zweier, Christiane Prof. Dr.
Medizinische Fakultät

Einrichtungen weiterer Autorinnen und Autoren

Leiden University
Regensburger Kinderzentrum St. Martin
Universität Zürich (UZH)


Hofmann, K., Zweier, M., Sticht, H., Zweier, C., Wittmann, W., Hoyer, J.,... Rauch, A. (2013). Biallelic SEMA3A defects cause a novel type of syndromic short stature. American Journal of Medical Genetics Part A, 161A(11), 2880-9.

Hofmann, Kristin, et al. "Biallelic SEMA3A defects cause a novel type of syndromic short stature." American Journal of Medical Genetics Part A 161A.11 (2013): 2880-9.


Zuletzt aktualisiert 2019-21-07 um 08:06