title: [Clinical and genetic study of Wilson's disease in affected twins and siblings].
abstract: OBJECTIVE
  To study the clinical and genetic characteristics of twins and siblings affected with Wilson's disease (WD).
  
  
  METHODS
  Clinical data and blood samples were collected from the subjects after informed consent was obtained. Genomic DNA was extracted and potential mutations in the exons in ATP7B gene were detected with PCR-DNA sequencing. Short tandem repeat (STR) genotyping was performed to determine the zygosity of the twins.
  
  
  RESULTS
  The 5 pairs of twins have all met the diagnostic criteria for WD. STR genotyping has confirmed that 4 pairs were monozygotic twins. 3 pairs of twins had an onset with liver symptoms, the other 2 had an onset with brain symptoms. ATP7B gene mutations were detected in 4 pairs of twins, which have all located in exons 8 and 13. A heterozygous p.R778W mutation in exon 8 and homozygous p.P992L mutation in exon 13 were detected in all patients from one family, whose parents have carried a heterozygous p.R778W mutation and p.P992L heterozygous mutation, respectively, which suggested loss of heterozygosity (LOH). In one family, no mutation was detected in all exons of the ATP7B gene in the patients and their parents. For a triplet, one female was with definite WD and brain symptoms at the onset, one male had subclinical type with WD, whilst another female was completely normal. The triplets and their mother have all carried a p.P992L heterozygous mutation .
  
  
  CONCLUSIONS
  Above results have confirmed an important role for genetic factors in the pathogenesis of WD. In addition to point mutations, LOH is also involved in the pathogenesis for WD.
authors.affiliation: Hospital Affiliated to Institute of Neurology, Anhui College of Traditional Chinese Medcine, Hefei, Anhui 230061, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Cheng
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.forename: Xuen
authors.initials: X
authors.lastname: Yu
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Zhou
authors.forename: Mingwei
authors.initials: M
authors.lastname: Gao
authors.forename: Rao
authors.initials: R
authors.lastname: Rao
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Hu
authors.forename: Renmin
authors.initials: R
authors.lastname: Yang
authors.forename: Yongzhu
authors.initials: Y
authors.lastname: Han
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D000073840:Copper-Transporting ATPases; D005091:Exons; D005260:Female; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D035781:Siblings; D014427:Twins; D055815:Young Adult
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases