A novel heterozygous mutation of three consecutive nucleotides causing Apert syndrome in a Congolese family.

Abstract

Apert syndrome (OMIM 101200) is a rare genetic condition characterized by craniosynostosis and syndactyly of hands and feet with clinical variability. Two single nucleotides mutations in the linker region between the immunoglobulin-like domains II and IIIa of the ectodomainin the Fibroblast Growth Factor Receptor 2 gene (FGFR2, OMIM 176943) are responsible of the vast majority of cases: c.755C > G; p.Ser252Trp (65%) and c.758C > G; p.Pro253Arg (34%. Three exceptional cases carry multiple substitutions of adjacent nucleotides in the linker region. Here we present a Congolese male patient and his mother, both affected with Apert syndrome of variable severity, carrying a previously undescribed heterozygous mutation of three consecutive nucleotides (c.756_758delGCCinsCTT) in the IgII-IgIIIa linker region. This is the fourth live-born patient to carry a multiple nucleotide substitution in the linker region and is the second alternative amino acid substitutions of the Pro253. Remarkably, this novel mutation was detected in the first Central African patient ever to be tested molecularly for the Apert syndrome. To discriminate between a hitherto unreported mutation and an ethnic specific polymorphism, we tested 105 Congolese controls, and no variation was detected.

• Authors: Aimé Lumaka, Gerrye Mubungu, Papino Mukaba, Pierre Mutantu, Gertrude Luyeye, Anniek Corveleyn, Bruno-Paul Tady, Prosper Lukusa Tshilobo, Koenraad Devriendt
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 57 Issue 4 Pg. 169-73 (Mar 2014) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 24486773 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• FGFR2 protein, human
• Receptor, Fibroblast Growth Factor, Type 2

Topics

• Acrocephalosyndactylia (diagnostic imaging, genetics)
• Adult
• Base Sequence
• Congo
• DNA Mutational Analysis
• Family Health
• Female
• Heterozygote
• Humans
• Infant
• Male
• Mutation
• Radiography
• Receptor, Fibroblast Growth Factor, Type 2 (genetics)