British Journal of Medicine and Medical Research, ISSN: 2231-0614,Vol.: 11, Issue.: 6
GLA Nonsense Mutation (c.485G>A) in a Three-Generation Family with Fabry’s Disease
Gabriela Sarca1, Cristina Dragomir2, Adriana Stan2 and Emilia Severin3* 1Professor C. Angelescu Hospital, Bucharest, Romania. 2Genetic Lab, Bucharest, Romania. 3Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
Gabriela Sarca1, Cristina Dragomir2, Adriana Stan2 and Emilia Severin3*
1Professor C. Angelescu Hospital, Bucharest, Romania.
2Genetic Lab, Bucharest, Romania.
3Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
(1) Paulo Ricardo Gazzola Zen, Departament of Clinical Medicine, Federal University of Health Sciences of Porto Alegre (UFCSPA), Brazil.
(1) Iman Mamdouh Talaat, Alexandria University, Egypt.
(2) Xu-jie Zhou, Peking University First Hospital, China.
Complete Peer review History: http://sciencedomain.org/review-history/11662
Background: GLA nonsense mutations seem to be associated with more severe clinical phenotype.
Aims: Main aims were to identify the disease-causing mutation, to screen high risk family members and to predict the severity of clinical phenotype and age of onset based on genotype-phenotype analysis.
Methods: Seven family members were clinically assessed and enzyme activity levels were evaluated as well. Genomic DNA was isolated from blood samples and analyzed for GLA gene mutation.
Results: The proband, a 34-year-old man, was misdiagnosed for years. At 25 years of age he was diagnosed with Fabry’s disease. He had a less severe phenotype failing to express cardiac, cerebral or renal symptoms. In addition, the patient presented a ventricular septal defect as an incidental finding which has not been reported previously in Fabry’s disease. His maternal uncle had a severe classic form and, in addition, osteonecrosis of femoral head rarely reported as associated findings. All females were heterozygous; 3 of them were asymptomatic and 2 developed milder symptoms, skin and heart predominantly affected. Fabry’s disease was caused by the presence of GLA nonsense mutation c.485G>A. All close relatives of proband had one copy of the mutation.
Conclusion: The family nonsense mutation c.485G>A known to predict the classic phenotype showed a wide range of clinical manifestations from severe to asymptomatic forms both in males and females supporting the intrafamilial phenotypic variability for Fabry’s disease.
Fabry’s disease; GLA gene; c.485G>A nonsense mutation; ventricular septal defect; intrafamilial phenotypic variability.
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DOI : 10.9734/BJMMR/2016/21432Review History Comments