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Three novel GJA1 missense substitutions resulting in oculo-dento-digital dysplasia (ODDD) - further extension of the mutational spectrum.
Gene. 2014 Apr 10; 539(1):157-61.GENE

Abstract

Oculodentodigital dysplasia (ODDD) is a clinically variable genetic disorder caused by mutations of the GJA1 gene, predominantly inherited in an autosomal dominant fashion. In rare cases ODDD can also exhibit autosomal recessive mode of inheritance. The phenotype of ODDD comprises craniofacial (short and narrow palpebral fissure, thin, narrow nose with hypoplastic alae nasi), dental (oligodontia, hypoplastic enamel), and digital abnormalities (syndactyly of finger 4/5, hypoplastic phalanges). Ocular manifestation is typical and involves microphthalmia, microcornea, glaucoma, congenital malformations of iris or vitreous, ectopic pupils or strabismus. To date, only 67 GJA1 mutations have been described to underlie ODDD and most of them (i.e. 97%) represent missense substitutions. In this report, we describe three (two familial and one sporadic) non-consanguineous cases presenting with ODDD features in whom we identified novel missense heterozygous mutations of the GJA1 gene: c.317T>G (p. L106R), c.G139C (p.D47H), and c.C257A (p.S86Y). The first two mutations were inherited from an affected parent, whereas the latter one occurred de novo. The mutations affect highly conserved amino acid residues located in the different portions of the GJA1 protein. Our report broadens the spectrum of probably pathogenic mutations associated with ODDD phenotype and demonstrates that the amino acid substitutions at highly conserved positions 47, 86, 106 may affect protein functioning and lead to the development of this syndrome. Together with molecular data, we provide a brief clinical description of the affected individuals.

Authors+Show Affiliations

Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland; NZOZ Center for Medical Genetics GENESIS, Poznan, Poland. Electronic address: jamsheer@wp.pl.Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.Department of Genetics, Wroclaw Medical University, Wroclaw, Poland.Genetic Services of Western Australia, King Edward Memorial Hospital for Women, Subiaco, Australia.Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland; NZOZ Center for Medical Genetics GENESIS, Poznan, Poland.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24508941

Citation

Jamsheer, Aleksander, et al. "Three Novel GJA1 Missense Substitutions Resulting in Oculo-dento-digital Dysplasia (ODDD) - Further Extension of the Mutational Spectrum." Gene, vol. 539, no. 1, 2014, pp. 157-61.
Jamsheer A, Sowińska-Seidler A, Socha M, et al. Three novel GJA1 missense substitutions resulting in oculo-dento-digital dysplasia (ODDD) - further extension of the mutational spectrum. Gene. 2014;539(1):157-61.
Jamsheer, A., Sowińska-Seidler, A., Socha, M., Stembalska, A., Kiraly-Borri, C., & Latos-Bieleńska, A. (2014). Three novel GJA1 missense substitutions resulting in oculo-dento-digital dysplasia (ODDD) - further extension of the mutational spectrum. Gene, 539(1), 157-61. https://doi.org/10.1016/j.gene.2014.01.066
Jamsheer A, et al. Three Novel GJA1 Missense Substitutions Resulting in Oculo-dento-digital Dysplasia (ODDD) - Further Extension of the Mutational Spectrum. Gene. 2014 Apr 10;539(1):157-61. PubMed PMID: 24508941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Three novel GJA1 missense substitutions resulting in oculo-dento-digital dysplasia (ODDD) - further extension of the mutational spectrum. AU - Jamsheer,Aleksander, AU - Sowińska-Seidler,Anna, AU - Socha,Magdalena, AU - Stembalska,Agnieszka, AU - Kiraly-Borri,Cathy, AU - Latos-Bieleńska,Anna, Y1 - 2014/02/06/ PY - 2013/11/13/received PY - 2014/01/26/revised PY - 2014/01/29/accepted PY - 2014/2/11/entrez PY - 2014/2/11/pubmed PY - 2014/4/23/medline KW - Connexin 43 KW - GJA1 KW - Missense mutation KW - ODDD KW - ODDS KW - Oculo-dento-digital dysplasia KW - Oculo-dento-osseous syndrome SP - 157 EP - 61 JF - Gene JO - Gene VL - 539 IS - 1 N2 - Oculodentodigital dysplasia (ODDD) is a clinically variable genetic disorder caused by mutations of the GJA1 gene, predominantly inherited in an autosomal dominant fashion. In rare cases ODDD can also exhibit autosomal recessive mode of inheritance. The phenotype of ODDD comprises craniofacial (short and narrow palpebral fissure, thin, narrow nose with hypoplastic alae nasi), dental (oligodontia, hypoplastic enamel), and digital abnormalities (syndactyly of finger 4/5, hypoplastic phalanges). Ocular manifestation is typical and involves microphthalmia, microcornea, glaucoma, congenital malformations of iris or vitreous, ectopic pupils or strabismus. To date, only 67 GJA1 mutations have been described to underlie ODDD and most of them (i.e. 97%) represent missense substitutions. In this report, we describe three (two familial and one sporadic) non-consanguineous cases presenting with ODDD features in whom we identified novel missense heterozygous mutations of the GJA1 gene: c.317T>G (p. L106R), c.G139C (p.D47H), and c.C257A (p.S86Y). The first two mutations were inherited from an affected parent, whereas the latter one occurred de novo. The mutations affect highly conserved amino acid residues located in the different portions of the GJA1 protein. Our report broadens the spectrum of probably pathogenic mutations associated with ODDD phenotype and demonstrates that the amino acid substitutions at highly conserved positions 47, 86, 106 may affect protein functioning and lead to the development of this syndrome. Together with molecular data, we provide a brief clinical description of the affected individuals. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/24508941/Three_novel_GJA1_missense_substitutions_resulting_in_oculo_dento_digital_dysplasia__ODDD____further_extension_of_the_mutational_spectrum_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(14)00138-3 DB - PRIME DP - Unbound Medicine ER -