Objective Microcephalia vera (MV) is a neurodevelopmental disorder characterised by a head circumference of three standard deviations below the mean (−3 SD) and non-progressive mental retardation. The MCPH1 gene product is microcephalin, supposed to control proliferation and differentiation of neuroblasts.

Methods Thirty-four patients with MV were enrolled at the Department of Pediatric Neurology, Hôpital R Debré, Paris, France and at the Department of Pediatrics, Federico II University, Naples, Italy. Inclusion criteria were: (1) head circumference <−3 SD at birth; (2) non-progressive mental retardation; (3) brain magnetic resonance imaging compatible with MV. Main exclusion criteria were: (1) intra-uterine exposure to toxins or infections; (2) chromosomal anomalies (by standard caryotype and multiplex ligation probe amplification for telomeric rearrangements). Molecular analysis was performed by direct sequencing of coding regions and intron–exon boundaries of MCPH1.

Results We found several polymorphisms of the MCPH1 gene in our patients. The following known polymorphisms G911T, G940C, A1175G, C1428T, G1782A were located in exon 8, whereas the C2226T, C2282T, C2418A polymorphisms were localised in exon 13. The G228T, G513T, C2045A and C2482T polymorphisms were found in exons 3, 6, 11 and 14, respectively. A previously unreported mutation, T783A, was found in two brothers affected by MV in the heterozygous state, associated with the G940A polymorphism.

Conclusions The MCPH1 gene is extremely rich in polymorphisms, which are particularly present in exon 8 and 13. The possible role of the T783A mutation in our two patients remains to be elucidated.