Estudos clÃnico-moleculares de trÃs famÃlias pernambucanas com microcefalia primÃria

AUTOR(ES)
DATA DE PUBLICAÇÃO

2004

RESUMO

Three consanguineous families from Pernambuco (families 1, 2 and 3) with primary autossomal recessive microcephaly were studied clinically, and two of them submitted to linkage analysis. Family 1, the largest one, had eight affected individuals (five males and three females, with ages varying between four and 27 years) with head circumference measurements 7-10 SD below the expected mean for age and sex. Family 2 had five microcephalic individuals (two males and three females with ages ranging from 14 to 25 years) with head circumference measurements 4 SD below the mean. In both families, microcephaly was accompanied by mental retardation of moderate severity and no other neurologic problem, dysmorphic feature or malformation. All the affected individuals were in good he alth and had growth parameters within normal limits. The parents had normal head circumference and intelligence. Ophthalmologic examination, standard lymphocyte karyotype (400 bands) and electroencephalogram performed in patients from both families were normal, and brain computed-tomography scan showed no cerebral malformations or neuronal ectopia. After exclusion of linkage to the five known loci related to autosomal recessive primary microcephaly, a genome trawl with 365 autosomal microssatelite markers spaced at approximately 10 cM intervals was performed in both kindreds. By autozygosity mapping a new locus (the sixth one, MCPH6 − microcephaly6) associated to autosomal recessive primary microcephaly was identified in family 1, but in family 2 no region of homozygosity was found. The third family (family 3), studied clinically but not submitted to linkage analysis, had a boy and a girl affected with head circumference measurements six and eight SD below the mean respectively. The boy presented mental retardation of moderate severity while the girl had severe neuropsychomotor delay, suggesting another disorder could be associated to primary microcephaly in this subject Their three siblings had head circumference measurements 2-3 SD below the expected mean (boderline for microcephaly), but only one of them had normal intelligence whislt the two others presented mental retardation of mild to moderate severity. The study of these three families resulted in the mapping of a novel locus (the sixth one) for autosomal recessive primary microcephaly and revealed that at least one more locus exist and awaits identification

ASSUNTO(S)

microcephaly mcph6 mapeamento por autozigose mcph6 microcefalia autozygosity mapping ciencias biologicas

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