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Neurofibromatosis von Recklinghausen type I phenotype and early onset of cancers in siblings compound heterozygous for mutations in MSH6
Author(s) -
Østergaard John R.,
Sunde Lone,
Okkels Henrik
Publication year - 2005
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.30998
Subject(s) - msh6 , neurofibromatosis , compound heterozygosity , mlh1 , msh2 , pms2 , mutation , medicine , genetics , biology , cancer research , dna mismatch repair , germline mutation , gene , dna repair
We report on a nonconsanguineous family in which two siblings with cutaneous manifestations leading to a diagnosis of neurofibromatosis type 1 (NF1) developed CNS tumors at an early age. In addition, one of them developed a T‐cell lymphoma. Neither parent had NF1. The mother was known to be heterozygous for a MSH6 mutation, and the father was found to be heterozygous for a different MSH6 mutation. Screening of MSH2, MLH1, MSH6, PMS1, PMS2 , and MLH3 in the affected children disclosed that they both were compound heterozygote for the MSH6 mutations of their parents. Most recently, about a dozen other cases of inherited bi‐allelic deficiency of mismatch repair (MMR) genes associated with early onset CNS tumors, hematologic malignancy, gastrointestinal neoplasia, café‐au‐lait spots, and other NF1 features have been reported. In the present study, we summarize the clinical findings of 27 individuals homozygous or compound heterozygous for an MMR gene mutation reported in the medical literature. We suggest that biparentally inherited mutations of one of the MMR genes should be considered in children with multiple café‐au‐lait spots who have early‐onset CNS tumors, hematologic malignancies, or early onset gastrointestinal neoplasia. © 2005 Wiley‐Liss, Inc.