Abstract
We report a consanguineous Pakistani family with seven affected individuals showing a syndromic form of congenital microcephaly. Clinical features of affected individuals include congenital microcephaly with sharply slopping forehead, moderate to severe mental retardation, anonychia congenita, and digital malformations. By screening human genome with microsatellite markers, this autosomal recessive condition was mapped to a 25.2 cM interval between markers D18S1150 and D18S1100 on chromosome 18p11.22-q12.3. However, the region of continuous homozygosity between markers D18S1150 and D18S997 spanning 15.33 cM, probably define the most likely candidate region for this condition. This region encompasses a physical distance of 12.03 Mb. The highest two-point LOD score of 3.03 was obtained with a marker D18S1104 and multipoint score reached a maximum of 3.43 with several markers. Six candidate genes, CEP76, ESCO1, SEH1L, TUBB6, ZNF519, and PTPN2 were sequenced, and were found to be negative for functional sequence variants.