OBJECTIVES: The objective of this study was to characterise Wilson's Disease (WD) [OMIM 277900] genetically and test for allelic variants in the copper transport gene (ATPase, Cu(++) transporting, beta polypeptide, ATP7B) responsible for the disease in an Omani family. METHODS: Three index patients from an Omani family had been previously diagnosed with WD. All three patients suffered neurological symptoms and signs. Forty-six relatives in the family were screened for WD. Eleven more individuals were positive, but asymptomatic. RESULTS: Thirteen non-disease-causing allelic gene variants, described previously, were identified in the ATP7B gene from 46 family members. A putative novel disease-causing splice-site variant (c.2866-2A>G), which has not been reported previously, was detected in this family. It is located upstream of exon 13 which encodes part of transmembrane copper channel (Ch/Tm6). Reverse transcription polymerase chain reaction was used to amplify a complementary DNA (cDNA) fragment containing exons 12, 13 and 14. Exon 13 was entirely skipped from the transcript which probably would result in a defective ATP7B protein. CONCLUSION: A new ATP7B splice-site allelic variant, found among the 14 WD patients segregated with the disease in a recessive manner, suggests it is a disease-causing variant.
OBJECTIVES: The objective of this study was to characterise Wilson's Disease (WD) [OMIM 277900] genetically and test for allelic variants in the copper transport gene (ATPase, Cu(++) transporting, beta polypeptide, ATP7B) responsible for the disease in an Omani family. METHODS: Three index patients from an Omani family had been previously diagnosed with WD. All three patients suffered neurological symptoms and signs. Forty-six relatives in the family were screened for WD. Eleven more individuals were positive, but asymptomatic. RESULTS: Thirteen non-disease-causing allelic gene variants, described previously, were identified in the ATP7B gene from 46 family members. A putative novel disease-causing splice-site variant (c.2866-2A>G), which has not been reported previously, was detected in this family. It is located upstream of exon 13 which encodes part of transmembrane copper channel (Ch/Tm6). Reverse transcription polymerase chain reaction was used to amplify a complementary DNA (cDNA) fragment containing exons 12, 13 and 14. Exon 13 was entirely skipped from the transcript which probably would result in a defective ATP7B protein. CONCLUSION: A new ATP7B splice-site allelic variant, found among the 14 WDpatients segregated with the disease in a recessive manner, suggests it is a disease-causing variant.
Authors: A B Shah; I Chernov; H T Zhang; B M Ross; K Das; S Lutsenko; E Parano; L Pavone; O Evgrafov; I A Ivanova-Smolenskaya; G Annerén; K Westermark; F H Urrutia; G K Penchaszadeh; I Sternlieb; I H Scheinberg; T C Gilliam; K Petrukhin Journal: Am J Hum Genet Date: 1997-08 Impact factor: 11.025
Authors: M S Nanji; V T Nguyen; J H Kawasoe; K Inui; F Endo; T Nakajima; T Anezaki; D W Cox Journal: Am J Hum Genet Date: 1997-06 Impact factor: 11.025
Authors: Mario Lovicu; Maria Barbara Lepori; Simona Incollu; Valentina Dessì; Antonietta Zappu; Raffaele Iorio; Mariangela D'Ambrosi; Maria Teresa Pellecchia; Paolo Barone; Giuseppe Maggiore; Stefano De Virgiliis; Antonio Cao; Georgios Loudianos Journal: Genet Test Mol Biomarkers Date: 2009-04
Authors: G Loudianos; V Dessì; M Lovicu; A Angius; A Nurchi; G C Sturniolo; M Marcellini; L Zancan; P Bragetti; N Akar; R Yagci; A Vegnente; A Cao; M Pirastu Journal: Hum Mutat Date: 1998 Impact factor: 4.878
Authors: A Figus; A Angius; G Loudianos; C Bertini; V Dessi; A Loi; M Deiana; M Lovicu; N Olla; G Sole Journal: Am J Hum Genet Date: 1995-12 Impact factor: 11.025