Delayed membranous ossification of the cranium associated with familial translocation (2;3)(p15;q12)

The relationship of delayed membranous cranial ossification to cranium bifi dum and parietal foramina syndromes is unclear, We report on a family with delayed cranial membranous ossification (OMIM 155980) that segregates with an apparently balanced reciprocal translocation between chromosomes 2 and 3 , The propositus had apparently low-set ears, proptosis, and a soft skull a t birth. A radiographic survey of the skeleton showed markedly decreased os sification of the cranial bones and no other skeletal abnormalities. The mo ther and maternal grandmother of the propositus have brachycephaly, hyperte lorism, and a history of a soft skull at birth. Chromosome analysis of peri pheral blood from the propositus showed 46,XY,t(2;3)(p15;q12). The proposit us, mother, and grandmother carry the same reciprocal translocation, wherea s the mother's two phenotypically normal sibs have a normal karyotype, We u sed an STS-linked BAC resource to define the translocation breakpoint by id entifying flanking BAC clones from both chromosomes 2, 1006D24 (D2S2279) an d 1060A5 (D2S2231), and chromosome 3, 3D17 (WI8558) and 3D18 [CITB Human BA C Library, J.R.K.]. This represents the second report of a family with dela yed membranous ossification of the cranium and the first report of the phen otype segregating with a chromosome rearrangement. Am. J. Med. Genet. 92:32 8-335, 2000. (C) 2000 Wiley-Liss, Inc.