Non-penetrance in a MODY 3 family with a mutation in the hepatic nuclear factor 1 alpha gene: implications for predictive testing

Z Miedzybrodzka, A T Hattersley, S Ellard, D Pearson, D de Silva, R Harvey, N Haites

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The most common cause of maturity-onset diabetes of the young (MODY) is a mutation in the hepatic nuclear factor 1 alpha (HNF1 alpha) gene (MODY3), We describe a family in which a missense mutation causing a Thr-Ile substitution at codon 620 has been found in all affected members, The mutation is not fully penetrant as two family members aged 87 and 46 have the mutation but do not have diabetes, The severity and age of diagnosis of diabetes varies widely within the family, and most presented over the age of 25, HNF1 alpha mutation screening should be considered in any family with autosomal dominant inheritance of diabetes where one member has presented with diabetes before the age of 25, Predictive testing is now possible within the majority of MODY families, and is of clinical benefit, but the possibility of non-penetrance should be addressed during counselling and interpretation of results.

Original languageEnglish
Pages (from-to)729-732
Number of pages4
JournalEJHG : European journal of human genetics : the official journal of the European Society of Human Genetics.
Volume7
Publication statusPublished - 1999

Keywords

  • diabetes
  • HNF1 alpha
  • maturity onset diabetes of the young
  • MODY
  • MODY3
  • predictive testing
  • YOUNG

Cite this

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title = "Non-penetrance in a MODY 3 family with a mutation in the hepatic nuclear factor 1 alpha gene: implications for predictive testing",
abstract = "The most common cause of maturity-onset diabetes of the young (MODY) is a mutation in the hepatic nuclear factor 1 alpha (HNF1 alpha) gene (MODY3), We describe a family in which a missense mutation causing a Thr-Ile substitution at codon 620 has been found in all affected members, The mutation is not fully penetrant as two family members aged 87 and 46 have the mutation but do not have diabetes, The severity and age of diagnosis of diabetes varies widely within the family, and most presented over the age of 25, HNF1 alpha mutation screening should be considered in any family with autosomal dominant inheritance of diabetes where one member has presented with diabetes before the age of 25, Predictive testing is now possible within the majority of MODY families, and is of clinical benefit, but the possibility of non-penetrance should be addressed during counselling and interpretation of results.",
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T1 - Non-penetrance in a MODY 3 family with a mutation in the hepatic nuclear factor 1 alpha gene: implications for predictive testing

AU - Miedzybrodzka, Z

AU - Hattersley, A T

AU - Ellard, S

AU - Pearson, D

AU - de Silva, D

AU - Harvey, R

AU - Haites, N

PY - 1999

Y1 - 1999

N2 - The most common cause of maturity-onset diabetes of the young (MODY) is a mutation in the hepatic nuclear factor 1 alpha (HNF1 alpha) gene (MODY3), We describe a family in which a missense mutation causing a Thr-Ile substitution at codon 620 has been found in all affected members, The mutation is not fully penetrant as two family members aged 87 and 46 have the mutation but do not have diabetes, The severity and age of diagnosis of diabetes varies widely within the family, and most presented over the age of 25, HNF1 alpha mutation screening should be considered in any family with autosomal dominant inheritance of diabetes where one member has presented with diabetes before the age of 25, Predictive testing is now possible within the majority of MODY families, and is of clinical benefit, but the possibility of non-penetrance should be addressed during counselling and interpretation of results.

AB - The most common cause of maturity-onset diabetes of the young (MODY) is a mutation in the hepatic nuclear factor 1 alpha (HNF1 alpha) gene (MODY3), We describe a family in which a missense mutation causing a Thr-Ile substitution at codon 620 has been found in all affected members, The mutation is not fully penetrant as two family members aged 87 and 46 have the mutation but do not have diabetes, The severity and age of diagnosis of diabetes varies widely within the family, and most presented over the age of 25, HNF1 alpha mutation screening should be considered in any family with autosomal dominant inheritance of diabetes where one member has presented with diabetes before the age of 25, Predictive testing is now possible within the majority of MODY families, and is of clinical benefit, but the possibility of non-penetrance should be addressed during counselling and interpretation of results.

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KW - HNF1 alpha

KW - maturity onset diabetes of the young

KW - MODY

KW - MODY3

KW - predictive testing

KW - YOUNG

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JO - EJHG : European journal of human genetics : the official journal of the European Society of Human Genetics.

JF - EJHG : European journal of human genetics : the official journal of the European Society of Human Genetics.

SN - 1018-4813

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