Genotype phenotype correlation in Wilson's disease within families-a report on four south Indian families  

作　　者：S Santhosh RV Shaji CE Eapen V Jayanthi S Malathi P Finny N Thomas M Chandy G Kurian GM Chandy 

机构地区：[1]Department of GI Sciences, Christian Medical College,Vellore, Tamil Nadu, India [2]Department of Haematology, Christian Medical College,Vellore, Tamil Nadu, India [3]Department of Medical Gastroenterology, Stanley Medical College, Chennai, Tamil Nadu, India [4]Department of Pediatrics, Institute of Child Health,Chennai, Tamil Nadu, India [5]Department of Endocrinology, Christian Medical College,Vellore, Tamil Nadu, India

出　　处：《World Journal of Gastroenterology》2008年第29期4672-4676,共5页世界胃肠病学杂志（英文版）

基　　金：The Department of Science and Technology, Government of India, under the fund number 22D187, 22D151;the Fluid research fund of Christian Medical College, Vellore-632004, Tamil Nadu, India

摘　　要：AIM: 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 classifi cation 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 identifi ed. 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.CONCLUSION: 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.AIM： 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 classifi cation 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 identifi ed. 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.CONCLUSION： 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.

关 键 词：Wilson＇s disease Genotype phenotypecorrelation 

分 类 号：R742.4[医药卫生—神经病学与精神病学]