Previously reported new type of autosomal recessive primary microcephaly is caused by compound heterozygous ASPM gene mutations

摘要

Autosomal recessive primary microcephaly (MCPH) delineates a genetically heterogeneous and rare subgroup of congenital microcephalies characterized by a pronounced reduction of brain volume at birth and intellectual disability.1-2 Genetic causes of MCPH subtypes 1-12 include mutations in genes encoding microcephalin (MCPH1; MIM*607117), WD-repeat-eontaining protein 62 (WDR62, MCPH2; MIM*613583), cyclin-dependent kinase 5 regulatory sub-unit-associated protein 2 (CDK5RAP2, MCPH3; MIM*608201), cancer susceptibility candidate 5 (CASC5, MCPH4; MIM*609173), abnormal spindle-like, microcephaly associated protein (ASPM, MCPH5; MIM*605481), cen-tromeric protein J (CENPJ, MCPH6; MIM*609279), SCL/TALl-interrupting locus (STIL, MCPH7; MIM*181590), , centrosomal protein 135 kD (CEP135, MCPH8; MIM*611423), centrosomal protein 152 kD (CEP152, MCPH9; MIM*613529), zinc finger protein 335 (ZNF335, MCPH10; MIM*610827), polyhomeotic-like 1 (PHC1, MCPH11; MIM*602978), and cyclin-dependent kinase 6 (CDK6; MCPH12, MIM*603368). A respectable percentage of families with an MCPH phe-notype do not carry mutations in the known MCPH genes, indicating further genetic heterogeneity.