+91 8617752708

British Journal of Medicine and Medical Research, ISSN: 2231-0614,Vol.: 11, Issue.: 6

Short Research Article

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.

Article Information
Editor(s):
(1) Paulo Ricardo Gazzola Zen, Departament of Clinical Medicine, Federal University of Health Sciences of Porto Alegre (UFCSPA), Brazil.
Reviewers:
(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

Abstracts

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.

Keywords :

Fabry’s disease; GLA gene; c.485G>A nonsense mutation; ventricular septal defect; intrafamilial phenotypic variability.

Full Article - PDF    Page 1-8

DOI : 10.9734/BJMMR/2016/21432

Review History    Comments

Our Contacts

Guest House Road, Street no - 1/6,
Hooghly, West Bengal,
India

+91 8617752708

 

Third Floor, 207 Regent Street
London, W1B 3HH,
UK

+44 20-3031-1429