A novel heterozygous mutation of three consecutive nucleotides causing Apert syndrome in a Congolese family.
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.
Centre for Human Genetics, University Hospitals, University of Leuven, P.O. Box 602, 3000 Leuven, Belgium; Center for Human Genetics, Faculty of Medicine, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, The Democratic Republic of the Congo; Department of Pediatrics, University Hospitals, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, The Democratic Republic of the Congo; INRB, Institut National de Recherche Biomedicale, P.O. Box, Kin I, Kinshasa, The Democratic Republic of the Congo.
Aimé
A
Lumaka
Center for Human Genetics, Faculty of Medicine, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, The Democratic Republic of the Congo; Department of Pediatrics, University Hospitals, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, The Democratic Republic of the Congo; INRB, Institut National de Recherche Biomedicale, P.O. Box, Kin I, Kinshasa, The Democratic Republic of the Congo.
Gerrye
G
Mubungu
Department of Surgery, University Hospitals, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, The Democratic Republic of the Congo.
Papino
P
Mukaba
Center for Human Genetics, Faculty of Medicine, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, The Democratic Republic of the Congo; INRB, Institut National de Recherche Biomedicale, P.O. Box, Kin I, Kinshasa, The Democratic Republic of the Congo.
Pierre
P
Mutantu
Department of Medical Imaging, Provincial General Hospital of Kinshasa, P.O. Box, Kin I, Kinshasa, The Democratic Republic of the Congo.
Gertrude
G
Luyeye
Centre for Human Genetics, University Hospitals, University of Leuven, P.O. Box 602, 3000 Leuven, Belgium.
Anniek
A
Corveleyn
Center for Human Genetics, Faculty of Medicine, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, The Democratic Republic of the Congo; Department of Pediatrics, University Hospitals, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, The Democratic Republic of the Congo.
Bruno-Paul
BP
Tady
Centre for Human Genetics, University Hospitals, University of Leuven, P.O. Box 602, 3000 Leuven, Belgium; Center for Human Genetics, Faculty of Medicine, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, The Democratic Republic of the Congo; Department of Pediatrics, University Hospitals, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, The Democratic Republic of the Congo; INRB, Institut National de Recherche Biomedicale, P.O. Box, Kin I, Kinshasa, The Democratic Republic of the Congo.
Prosper
P
Lukusa Tshilobo
Centre for Human Genetics, University Hospitals, University of Leuven, P.O. Box 602, 3000 Leuven, Belgium. Electronic address: koenraad.devriendt@uzleuven.be.
Koenraad
K
Devriendt
D000168:Acrocephalosyndactylia / Q000000981:diagnostic imaging / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D003223:Congo; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011859:Radiography; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*
C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2
Apert syndrome; Central Africa; Craniosynostosis; Syndactyly; Tandem base substitution