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

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.

Nuclear medicine imaging in osteonecrosis of hip:Old and current concepts

Osteonecrosis(ON) is caused by inadequate blood supply leading to bone death, which results in the collapse of the architectural bony structure. Femoral head is the most common site involved in ON. Magnetic resonance imaging(MRI) is a commonly used imaging modality to detect early ON. When MRI is inconclusive, bone scan is helpful in detecting ON during early phase of the disease. As newer nuclear medicine equipment, like single photon emission computed tomography/computed tomography(CT) and positron emission tomography/CT, are emerging in medical science, we review the role of these imaging modalities in ON of femoral head.