RESUMO
Primary microcephaly is a clinical diagnosis made when an individual has a head circumference of greater than 3 standard deviations below the age and sex matched population mean, mental retardation but without other associated malformations and no apparent aetiology. The majority of cases of primary microcephaly exhibit an autosomal recessive mode of inheritance. We now demonstrate the genetic heterogeneity of this condition with the identification of a second primary microcephaly locus (MCPH2) on chromosome 19q13.1-13.2 in two multi-affected consanguineous families. The minimum critical region containing the MCPH2 locus is defined by the polymorphic markers D19S416 and D19S420 spanning a region of approximately 7.6 cM.
Assuntos
Cromossomos Humanos Par 19/genética , Genes Recessivos , Ligação Genética/genética , Microcefalia/genética , Adolescente , Mapeamento Cromossômico , Família , Homozigoto , Humanos , MasculinoRESUMO
Primary (or "true") microcephaly is inherited as an autosomal recessive trait and is thought to be genetically heterogeneous. Using autozygosity mapping, we have identified a genetic locus (MCPH1) for primary microcephaly, at chromosome 8p22-pter, in two consanguineous families of Pakistani origin. Our results indicate that the gene lies within a 13-cM region between the markers D8S1824 and D8S1825 (maximum multipoint LOD score of 8.1 at D8S277). In addition, we have demonstrated the genetic heterogeneity of this condition by analyzing a total of nine consanguineous families with primary microcephaly.
