title: 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). Of these, 12 mutations have not been previously reported. The p.N1270S, p.C703Y, IVS18-2A > G, p.R1319X, c.2304-2305insC, and p.H1069Q were present in 7.8%, 6.2%, 6.2%, 6.2%, 4.7%, and 4.7%, respectively, of studied chromosomes in independent families. One patient was homozygous for both p.N1270S and p.T1434M mutations. Frameshift and nonsense mutations were found in 50% of patients with disease onset < or =8 years compared with only 26% in patients with onset >8 years. Despite mutation heterogeneity in Egyptian children, genotype-phenotype correlation analysis seems to be promising in this population, as many patients carry homozygous mutations, a situation that mandates a larger-scale population screening to identify the carrier rate in this community.
authors.affiliation: Pediatrics Department, Ain Shams University, Cairo, Egypt. tyghaffar@gmail.com.|Yassin Abdelghaffar Charity Center for Liver Disease and Research, 6 Emarat El Tasniea St. From Makram Abied, Nasr Citry, Cairo, Egypt. tyghaffar@gmail.com.
authors.forename: Tawhida Y
authors.initials: TY
authors.lastname: Abdelghaffar
authors.affiliation: Pediatrics Department, Ain Shams University, Cairo, Egypt.|Yassin Abdelghaffar Charity Center for Liver Disease and Research, 6 Emarat El Tasniea St. From Makram Abied, Nasr Citry, Cairo, Egypt.|Medical Genetics Center, 27A Baghdad Street, Korba, Cairo, Egypt.
authors.forename: Solaf M
authors.initials: SM
authors.lastname: Elsayed
authors.affiliation: Pediatrics Department, Ain Shams University, Cairo, Egypt.|Medical Genetics Center, 27A Baghdad Street, Korba, Cairo, Egypt.
authors.forename: Ezzat
authors.initials: E
authors.lastname: Elsobky
authors.affiliation: Med. Klinik Gastroenterologie, Hepatologie u. Endokrinologie, Charité Campus Mitte and Transplantationshepatologie, Münster, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Bochow
authors.affiliation: Med. Klinik Gastroenterologie, Hepatologie u. Endokrinologie, Charité Campus Mitte and Transplantationshepatologie, Münster, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Büttner
authors.affiliation: Med. Klinik Gastroenterologie, Hepatologie u. Endokrinologie, Charité Campus Mitte and Transplantationshepatologie, Münster, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schmidt
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D019943:Amino Acid Substitution; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D004534:Egypt; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D017384:Sequence Deletion
chemical_list: D027682:Cation Transport Proteins; D018389:Codon, Nonsense; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases