RESUMO
Juvenile polyposis syndrome (JPS) is an inherited hamartomatous-polyposis syndrome with a risk for colon cancer. JPS is a clinical diagnosis by exclusion, and, before susceptibility genes were identified, JPS could easily be confused with other inherited hamartoma syndromes, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Cowden syndrome (CS). Germline mutations of MADH4 (SMAD4) have been described in a variable number of probands with JPS. A series of familial and isolated European probands without MADH4 mutations were analyzed for germline mutations in BMPR1A, a member of the transforming growth-factor beta-receptor superfamily, upstream from the SMAD pathway. Overall, 10 (38%) probands were found to have germline BMPR1A mutations, 8 of which resulted in truncated receptors and 2 of which resulted in missense alterations (C124R and C376Y). Almost all available component tumors from mutation-positive cases showed loss of heterozygosity (LOH) in the BMPR1A region, whereas those from mutation-negative cases did not. One proband with CS/CS-like phenotype was also found to have a germline BMPR1A missense mutation (A338D). Thus, germline BMPR1A mutations cause a significant proportion of cases of JPS and might define a small subset of cases of CS/BRRS with specific colonic phenotype.
Assuntos
Anormalidades Múltiplas/genética , Mutação em Linhagem Germinativa/genética , Síndrome do Hamartoma Múltiplo/genética , Pólipos Intestinais/genética , Proteínas Serina-Treonina Quinases , Receptores de Fatores de Crescimento , Receptores de Fatores de Crescimento Transformadores beta/genética , Anormalidades Múltiplas/fisiopatologia , Receptores de Proteínas Morfogenéticas Ósseas Tipo I , Neoplasias do Colo/complicações , Neoplasias do Colo/genética , Análise Mutacional de DNA , Genótipo , Síndrome do Hamartoma Múltiplo/complicações , Síndrome do Hamartoma Múltiplo/fisiopatologia , Humanos , Pólipos Intestinais/complicações , Pólipos Intestinais/fisiopatologia , Perda de Heterozigosidade/genética , Repetições de Microssatélites/genética , Fenótipo , Receptores de Fatores de Crescimento Transformadores beta/química , SíndromeRESUMO
We report on a girl with duplication of 6q22.32 --> qter and microcephaly, frontal bossing, facial anomalies, and webbed neck. She has congenital heart disease, renal hypoplasia, and hearing loss along with severe developmental delay. Published reports of seven other patients are reviewed and compared. The most frequent anomalies include microcephaly, abnormal face, webbed neck, congenital heart disease, limb contractures, and developmental delay.
