A novel splice-site allelic variant is responsible for Wilson Disease in an Omani family

Mohammed Al-Tobi, Masoud Kashoob, Surendranath Joshi, Riad Bayoumi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)357-362
Number of pages6
JournalSultan Qaboos University Medical Journal
Volume11
Issue number3
Publication statusPublished - Aug 2011

Fingerprint

Hepatolenticular Degeneration
Exons
Copper
Genes
Genetic Databases
Reverse Transcription
Signs and Symptoms
Adenosine Triphosphatases
Complementary DNA
Polymerase Chain Reaction
Peptides
Proteins

Keywords

  • Allelic Variant
  • ATP7B
  • Copper
  • Mutation
  • Oman
  • Splice site
  • Wilson Disease

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A novel splice-site allelic variant is responsible for Wilson Disease in an Omani family. / Al-Tobi, Mohammed; Kashoob, Masoud; Joshi, Surendranath; Bayoumi, Riad.

In: Sultan Qaboos University Medical Journal, Vol. 11, No. 3, 08.2011, p. 357-362.

Research output: Contribution to journalArticle

Al-Tobi, Mohammed ; Kashoob, Masoud ; Joshi, Surendranath ; Bayoumi, Riad. / A novel splice-site allelic variant is responsible for Wilson Disease in an Omani family. In: Sultan Qaboos University Medical Journal. 2011 ; Vol. 11, No. 3. pp. 357-362.
@article{2fb9c1ecad644567a48eeb756164916f,
title = "A novel splice-site allelic variant is responsible for Wilson Disease in an Omani family",
abstract = "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.",
keywords = "Allelic Variant, ATP7B, Copper, Mutation, Oman, Splice site, Wilson Disease",
author = "Mohammed Al-Tobi and Masoud Kashoob and Surendranath Joshi and Riad Bayoumi",
year = "2011",
month = "8",
language = "English",
volume = "11",
pages = "357--362",
journal = "Sultan Qaboos University Medical Journal",
issn = "2075-051X",
publisher = "Sultan Qaboos University",
number = "3",

}

TY - JOUR

T1 - A novel splice-site allelic variant is responsible for Wilson Disease in an Omani family

AU - Al-Tobi, Mohammed

AU - Kashoob, Masoud

AU - Joshi, Surendranath

AU - Bayoumi, Riad

PY - 2011/8

Y1 - 2011/8

N2 - 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.

AB - 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.

KW - Allelic Variant

KW - ATP7B

KW - Copper

KW - Mutation

KW - Oman

KW - Splice site

KW - Wilson Disease

UR - http://www.scopus.com/inward/record.url?scp=80052708822&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052708822&partnerID=8YFLogxK

M3 - Article

VL - 11

SP - 357

EP - 362

JO - Sultan Qaboos University Medical Journal

JF - Sultan Qaboos University Medical Journal

SN - 2075-051X

IS - 3

ER -