title: Genotype phenotype correlation in Wilson's disease within families--a report on four south Indian families.
abstract: OBJECTIVE
  To study the genotype phenotype correlation in Wilson's disease (WD) patients within families.
  
  
  METHODS
  We report four unrelated families from South India with nine members affected with WD. Phenotype was classified as per international consensus phenotypic classification of WD. DNA was extracted from peripheral blood and 21 exons of ATP7B gene and flanking introns were amplified by polymerase chain reaction (PCR). The PCR products were screened for mutations and the aberrant products noted on screening were sequenced.
  
  
  RESULTS
  Four separate ATP7B mutations were found in the four families. ATP7B mutations were identical amongst affected members within each family. Three families had homozygous mutations of ATP7B gene while one family had compound heterozygous mutation, of which only one mutation was identified. We noted concordance between ATP7B gene mutation and Wilson's disease phenotype amongst members within each family. The age of onset of symptoms or of detection of asymptomatic disease, baseline serum ceruloplasmin and baseline urinary copper levels were also similar in affected members of each family. Minor differences in phenotype and baseline serum ceruloplasmin level were noted in one family.
  
  
  CONCLUSIONS
  We report concordance between ATP7B mutation and WD phenotype within each family with > 1 member affected with WD. Homozygous ATP7B mutation was present in 3 of the 4 families studied. Our report supports allelic dominance as a determinant of WD phenotype. However, in one family with compound heterozygous mutation, there was a similar WD phenotype which suggests that there may be other factors determining the phenotype.
authors.affiliation: Department of Gastrointestinal Sciences Christian Medical College, Vellore, Tamil Nadu, India. santhoshcmc@yahoo.com
authors.forename: S
authors.initials: S
authors.lastname: Santhosh
authors.forename: R V
authors.initials: RV
authors.lastname: Shaji
authors.forename: C E
authors.initials: CE
authors.lastname: Eapen
authors.forename: V
authors.initials: V
authors.lastname: Jayanthi
authors.forename: S
authors.initials: S
authors.lastname: Malathi
authors.forename: P
authors.initials: P
authors.lastname: Finny
authors.forename: N
authors.initials: N
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Chandy
authors.forename: G
authors.initials: G
authors.lastname: Kurian
authors.forename: G M
authors.initials: GM
authors.lastname: Chandy
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000483:Alleles; D027682:Cation Transport Proteins / Q000235:genetics; D002648:Child; D000073840:Copper-Transporting ATPases; D005260:Female; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000208:ethnology* / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases