Mutational analysis of ATP7B gene in Egyptian children with Wilson disease: 12 novel mutations

Abstract

The aim of this work was to study the mutations within ATP7B in Egyptian children with Wilson disease and to evaluate any potential correlation between genotype and phenotype in this cohort. The study consisted of 48 children with Wilson disease from 32 independent families. The 21 exons of the ATP7B gene were amplified in a thermal cycler. Direct sequencing of the amplified polymerase chain reaction (PCR) products was performed by cycle sequencing using fluorescent dye terminators in an automatic ABI sequencer. Thirty-one different mutations in 96 chromosomes were detected (19 missense, three nonsense, seven frameshift deletions, and two splice-site mutations).

Wilson Disease Mutations in the American Population: Identification of Five Novel Mutations in ATP7B

“…In addition to these two common mutations, many other rare mutations tend to have regional clustering [7]. N1270S, however, is distinguished by its common occurrence in a large number of groups, including our American cohort, Chinese [12,13] Egyptian [19], Brazilian [20], Italian and Turkish [21], and American [9] groups. The frequency of this mutation among diverse ethnic groups suggests that this residue may represent a hot spot for mutation.…”

Role of genotyping in Wilson’s disease

“…Interestingly, in children presenting with hepatic WD the chance of identifying disease causing mutations is up to 100%. Regional clustering of mutations has been very well established [23][24][25][26][27][28][29]. This makes it possible to use genetic diagnostics for regional screening programs.…”

Common local founder effects for Wilson's disease and hereditary hemochromatosis; mutation studies of a large family

“…We can hardly claim such a history of the present area near the northern edge of the inhabited world (28). The H1069Q/R1319X in XIII:3 ( Figure 3) has been reported from Kalymnos [7] and Egypt [29], while the neighbor mutations, XIII:2 (W779X/W779X) and XIII:4 (T977M) have been reported from Austria and Hungary [30]. The multitude of mutations may indicate that this northern outpost has not been as isolated as thought.…”