Figure 1.

Pedigrees and clinical features of patients. (A) Pedigrees of families manifesting primary microcephaly and Seckel syndrome carrying homozygous loss-of-function mutations in ASPM and CENPJ (shown in black beneath symbols), respectively, and heterozygous mutations in the proposed modifier genes (shown in red above the symbols). Affected members of family 5 were found mutated only for CENPJ but not for PCNT. (B) Photos of the selected individuals belong to the five families. Notably, joint contractures are clearly visible in photos of the affected members, V-1 and V-9, of family 1. Family 4 (V-6, V-7 and V-8) and family 5 feature Seckel syndrome whereas patients in the left loop of family 4 (VI-2, VI-3, VI-3 and VI-5) are clinically diagnosed with MOPDII. White arrowheads shown on the forehead areas of V-6 and V-7 of family 4 indicate hypopigmentation.