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D. Rivera, J. C. Zenteno, D. Campos, A. Gonzalez-del Angel; Novel R76C Mutation in Connexin 43 Causing Oculodental Digital Dysplasya Without Dental Involvement. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1647.
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Oculodentodigital Dysplasia (ODDD) is an autosomal dominant syndrome characterized by facial, ocular (microcornea, microftalmia, glaucoma,cataract), dental , and limb abnormalities.Mutations in the gene GJA1 have been recognized as responsible for ODDD and approximately 83 mutations have been described to date in subjects with ODDD. GJA1 encodes Cx43 (Connexin 43) protein, whose major function is as part of the gap junctions of cell-to-cell channels. There is no clear genotype-phenotype correlation in ODDD and clinical variability is common.We present an ODDD case without dental involvement in which a novel GJA1mutation was demonstrated.
The propositus is a 8-year old girl, born from a non-consanguinity couple. No exposure to teratogens was recorded. The patient had mild psychomotor retardation and seizures. On physical examination the patient had normal weight and height, cephalic perimeter below normal, brachycephaly, wide nasal bridge, epicanthal folds, brachydactily and clinodactily of the 5th finger in both hands, bilateral cutaneous syndactily of the 2nd, 3rd and 4th fingers in feet.No teeth abnormalities were present. A segmentation defect of T2-T3 vertebrae was identified on X-rays. Severe right hypoacusia was documented. She had a best corrected visual acuity of 20/40 OD, 20/30 OS, and bilateral microcornea (9 mm). IOP was normal. The 2 exons of GJA1 were amplified by PCR and directly sequenced in forward and reverse directions in DNA from the propositus and her parents.
A novel heterozygous mutation of C>T at GJA1 nucleotide 226 (c.226C>T) was demonstrated in DNA from the patient. This change predicts a missense mutation from arginine (CGC) to cysteine (TGC) in residue number 76 (R76C) of Cx 43. Parental DNA analysis did not demonstrated the mutation.
To the best of our knowledge the R76C mutation has not been described before in ODDD. Other two mutations have been found in this codon, but they were from Arginine to other aminoacids different from cysteine, (R76H, R76S), suggesting that this could be a mutational hot spot. It is remarkable that no teeth abnormalities were found in the patient, as these abnormalities are one of the most common among patients with ODDD. Our findings adds to the mutational spectrum in ODDD and supports the already observed wide clinical variability of the disease.
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