Back to Search Start Over

Homozygous PMS2 germline mutations in two families with early-onset haematological malignancy, brain tumours, HNPCC-associated tumours, and signs of neurofibromatosis type 1.

Authors :
Krüger, Stefan
Kinzel, Miriam
Walldorf, Constanze
Gottschling, Sven
Bier, Andrea
Tinschert, Sigrid
von Stackelberg, Arend
Henn, Wolfram
Görgens, Heike
Boue, Stephanie
Kölble, Konrad
Büttner, Reinhard
Schackert, Hans K.
Source :
European Journal of Human Genetics. Jan2008, Vol. 16 Issue 1, p62-72. 11p. 3 Color Photographs, 2 Diagrams, 2 Charts.
Publication Year :
2008

Abstract

Heterozygous germline mutations in mismatch repair (MMR) genes MLH1, PMS2, MSH2, and MSH6 cause Lynch syndrome. New studies have indicated that biallelic mutations lead to a distinctive syndrome, childhood cancer syndrome (CCS), with haematological malignancies and tumours of brain and bowel early in childhood, often associated with signs of neurofibromatosis type 1. We provide further evidence for CCS reporting on six children from two consanguineous families carrying homozygous PMS2 germline mutations. In family 1, all four children had the homozygous p.I590Xfs mutation. Two had a glioblastoma at the age of 6 years and one of them had three additional Lynch-syndrome associated tumours at 15. Another sibling suffered from a glioblastoma at age 9, and the fourth sibling had infantile myofibromatosis at 1. In family 2, two of four siblings were homozygous for the p.G271V mutation. One had two colorectal cancers diagnosed at ages 13 and 14, the other had a Non-Hodgkin's lymphoma and a colorectal cancer at ages 10 and 11, respectively. All children with malignancies had multiple café-au-lait spots. After reviewing published cases of biallelic MMR gene mutations, we provide a concise description of CCS, revealing similarities in age distribution with carriers of heterozygous MMR gene mutations.European Journal of Human Genetics (2008) 16, 62–72; doi:10.1038/sj.ejhg.5201923; published online 12 September 2007 [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10184813
Volume :
16
Issue :
1
Database :
Academic Search Index
Journal :
European Journal of Human Genetics
Publication Type :
Academic Journal
Accession number :
27879615
Full Text :
https://doi.org/10.1038/sj.ejhg.5201923