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Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes
Author(s) -
Menko FH,
Kneepkens CMF,
De Leeuw N,
Peeters EAJ,
Van Maldergem L,
Kamsteeg EJ,
Davidson R,
Rozendaal L,
Lasham CA,
PeetersScholte CMP,
Jansweijer MC,
HilhorstHofstee Y,
Gille JJP,
Heins YM,
Nieuwint AWM,
Sistermans EA
Publication year - 2008
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2008.01026.x
Subject(s) - macrocephaly , pten , haploinsufficiency , phenotype , genetics , biology , colorectal cancer , medicine , cancer , gene , apoptosis , pi3k/akt/mtor pathway
Infantile juvenile polyposis is a rare disease with severe gastrointestinal symptoms and a grave clinical course. Recently, 10q23 microdeletions involving the PTEN and BMPR1A genes were found in four patients with infantile juvenile polyposis. It was hypothesized that a combined and synergistic effect of the deletion of both genes would explain the condition. Subsequently, however, a patient with a larger 10q23 deletion including the same genes but with a mild clinical phenotype was identified. Here, we present four additional patients with 10q23 microdeletions involving the PTEN and BMPR1A genes. The sizes of the deletions were analyzed using single nucleotide polymorphism array analysis. All patients had macrocephaly, dysmorphic features, retardation and congenital abnormalities. One patient developed colorectal cancer. However, only one case had disease onset before 2 years of age and severe symptoms requiring colectomy. No clear correlation was found between ages at onset or severity of gastrointestinal symptoms and the sizes of the deletions. We conclude that patients with 10q23 microdeletions involving the PTEN and BMPR1A genes have variable clinical phenotypes, which cannot be explained merely by the deletion sizes. The phenotypes are not restricted to severe infantile juvenile polyposis but include childhood‐onset cases with macrocephaly, retardation, mild gastrointestinal symptoms and possibly early‐onset colorectal cancer.