Two novel GJA1 variants in oculodentodigital dysplasia. Issue 9 (25th July 2019)

• Record Type: Journal Article
• Authors: Pace, Nikolai P.; Benoit, Valerie; Agius, David; Grima, Maria Angela; Parascandalo, Raymond; Hilbert, Pascale; Borg, Isabella
• Is Part Of: Molecular genetics & genomic medicine. Volume 7:Issue 9(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-07-25
• Subjects: connexin 43 -- GJA1 gene -- oculodentodigital dysplasia; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.882
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: Oculodentodigital dysplasia (ODDD) is a rare disorder with pleiotropic effects involving multiple body systems, caused by mutations in the gap junction protein alpha 1 ( GJA1 ) gene. GJA1 gene encodes a polytopic connexin membrane protein, Cx43, that is a component of connexon membrane channels. Methods: We describe two unrelated female probands referred for a genetic review in view of a dysmorphic clinical phenotype. Results: Two novel missense mutations in GJA1 that substitute conserved amino acids in the first and second transmembrane domains (NM_000165.5: c.77T>C p.Leu26Pro and NM_000165.5:c.287T>G p.Val96Gly) were detected through targeted sequencing of GJA1 . These variants were detected in the heterozygous state in the two Maltese probands and segregated with the disease phenotype. Conclusion: This report further expands the mutational spectrum of ODDD. Abstract : This article describes two novel damaging missense mutations in GJA1 and the accompanying clinical phenotypes in two unrelated Maltese probands with Oculodentodigital dysplasia (ODDD). This report expands on the spectrum of mutations that have been described in the context of ODDD.