RESUMO
Familial adenomatous polyposis (FAP) is an inherited colon cancer syndrome caused by mutations in the APC gene on chromosome region 5q21. Patients typically present with several hundred to several thousand polyps throughout the colon. Benign and malignant extracolonic manifestations are often present. Attenuated FAP (AFAP) is a recognized variant of FAP in which patients present with fewer than 100 polyps and appear to have a delayed onset of the clinical manifestations of FAP. Mutations in specific regions of the APC gene are associated with AFAP. A full deletion of the APC gene region has previously been thought to be associated with typical FAP. We now report on a 39-year-old man with a cytogenetically visible interstitial 5q deletion. Fluorescent in situ hybridization analysis with two cosmid probes specific for the 5' and 3' ends of the gene indicated that the entire APC locus is deleted. The number of polyps (50-60) seen in this patient was consistent with AFAP, as was the absence of multiple congenital hypertrophy of the retinal pigment epithelium (CHRPE). This is the first reported case of AFAP associated with a germline deletion of the entire APC gene.
Assuntos
Polipose Adenomatosa do Colo/genética , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Adulto , Bandeamento Cromossômico , Citogenética , Genes APC , Mutação em Linhagem Germinativa , Humanos , Hibridização in Situ Fluorescente , Masculino , Epitélio Pigmentado Ocular/anormalidadesRESUMO
Sixty-one sequential patients initially referred because of hand-reduction abnormalities were retrospectively reviewed. Twenty distinct diagnoses were recognized. Particularly noteworthy was the number of instances in which standard classification schemes failed to explain fully the structural or syndromic characteristics in this group of patients. One-fourth (15 of 61) of the diagnoses were of disorders resulting from abnormalities of single genes; more than one-third (21 of 61) had multiple malformation syndromes. The importance of dysmorphologic and genetic investigation of individuals with congenital reduction malformations of the hands is evident from these data and from the cases presented.
Assuntos
Anormalidades Múltiplas/genética , Doenças do Desenvolvimento Ósseo/genética , Deformidades Congênitas da Mão , Adolescente , Adulto , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
A family with four members with split foot/split hand malformations and congenital nystagmus is described. The clinical characteristics in this family correspond to those seen in two other families previously reported. Taken together, these three families suggest that a single, pleiotropic dominant gene is causal. Karsch-Neugebauer syndrome is suggested as an appropriate eponymic designation for this disorder.
