DNA linkage based diagnosis of Wilson disease in asymptomatic siblings
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
DNA linkage based diagnosis of Wilson disease in asymptomatic
siblings
|
|
| Creator |
Gupta, Arnab
Neogi, R Mukherjea, M Mukhopadhyay, A Roychoudhury, Susanta Senapati, A Gangopadhyay, Prasanta K Ray, Kunal |
|
| Subject |
Molecular & Human Genetics
|
|
| Description |
Wilson disease (WD) is an autosomal recessive disorder caused by defects in
ATP7B gene located in chromosome 13q14, and manifested as hepatolenticular degeneration as a
result of accumulation of copper. No information on the mutation in the ATP7B gene and haplotypes
using linked markers is available for WD patients in India. Hence, the present study was undetaken
to identify, by a PCR-based molecular diagnostic test, presymptomatic siblings of WD affected individuals
in families with multiple offspring.
Methods: Genomic DNA was prepared from the peripheral blood of the patients, siblings and his/her
first degree relatives. The repeat-markers flanking WD locus were amplified by PCR using fluorescent
labeled primers. Amplified DNA fragments were analyzed by polyacrylamide gel electrophoresis in
ABI 377 DNA sequencing system. Genotypes of the samples were determined using Genescan software.
Haplotypes were determined based on segregation of the alleles in the families under study.
Results: Among 15 WD affected families with multiple children, 4 cases were identified where younger
siblings shared same genotype as the patient at all three markers analyzed. Further, eight different
haplotypes were detected in the four patients.
Interpretation & conclusion: The siblings of the WD patients carrying the same genotype at the markers
linked to WD locus were presymptomatically diagnosed individuals. Presence of eight different
haplotypes in the four patients suggested mutational heterogeneity at the WD locus. The test helps
clinicians for therapeutic intervention in suspect WD cases by copper chelating agents prior to
manifestation of overt clinical symptoms.
Key words ATP7B - genotype - haplotype - microsatellite -
Wilson disease (WD) is a genetic disorder, which
manifests as hepatolenticular degeneration as a result of
accumulation of copper in the brain, liver, kidney and cornea due to its deranged biliary excretion1. In 1912, a WD was described as a familial syndrome of progressive lenticular degeneration associated with cirrhosis of the liver2. The etiological role of copper in the pathogenesis of WD was recognized much later
|
|
| Date |
2003
|
|
| Type |
Article
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/1078/1/17_IJMR_2003.pdf
Gupta, Arnab and Neogi, R and Mukherjea, M and Mukhopadhyay, A and Roychoudhury, Susanta and Senapati, A and Gangopadhyay, Prasanta K and Ray, Kunal (2003) DNA linkage based diagnosis of Wilson disease in asymptomatic siblings. Indian Journal of Medical Research, 118 (11). pp. 208-214. |
|
| Relation |
http://icmr.nic.in/ijmr/2003/1106.pdf
http://www.eprints.iicb.res.in/1078/ |
|