A novel locus for parietal foramina maps to chromosome 4q21-q23

Parietal foramina [PFM], inherited usually in an autosomal dominant mode, is an extremely rare developmental defect characterized by a symmetrical, oval hole in the parietal bone. It can be present as either an isolated or a syndromic feature. PFM types 1 and 2 (PFM1 and PFM2) have been found to be caused by mutations in the MSX2 and ALX4 genes, located to chromosomes 5 and 11, respectively. After exclusion of both the above loci in a large Chinese pedigree with autosomal dominant PFM, a genome-wide search revealed a linkage of the PFM to markers at the 4q21-q23 region. The maximum LOD score from two-point linkage analysis is 3.87 for marker D4S2961. Analysis of co-segregated haplotype localized the region to a 20-cM interval that flanks D4S392 and D4S2945. Therefore, we concluded that the PFM in the family is a new PFM locus. Although three genes, BMPR1B, PP1 and IBSP, are located to 4q21-q25 and their functions are related to bone morphogenesis, no mutations were identified by sequencing analysis of their exons.