Molecular and cytogenetic analysis of familial Xp deletions

Five families in which an Xp deletion is segregating and two families in which an X chromosome rearrangement including a deletion of the short arm is segregating were ascertained for study. Normal fertility was seen in all families. Members from 5 of the 7 families manifested short stature (height <5th centile), while normal height was present in two families. Studies of both the FMR-1 and the androgen receptor loci using PCR based X-inactivation analysis demonstrated that in all families analyzed, there is preferential inactivation of one X chromosome. Molecular cytogenetic analysis showed that members of 3 of the 7 families share a common breakpoint in an approximate 2-3 Mb region at Xp22.12, suggesting a possible hotspot for chromatin breakage. Previous genotype-phenotype correlations and deletion mapping have indicated that a gene for stature resides within the pseudoautosomal region in Xp22.33. Our findings indicate that the loss of this region is not always associated with short stature, suggesting that other factors may be involved.