Detection of gene deletions in children with chondrodysplasia punctata, ichthyosis, Kallmann syndrome, and ocular albinism by FISH studies.

BACKGROUND

Contiguous gene syndrome (CGS) is characterized by a series of clinical features resulting from interstitial or terminal deletions of various adjacent genes. Several important genes have been identified in the Xp22.3 region to be responsible for genetically heterogeneous diseases. In this study, fluorescence in situ hybridization (FISH) methods were used to detect the extent of gene deletion related to the phenotypes of patients with Xp-CGS.

METHODS

The molecular cytogenetic statuses of 23 boys with at least 1 apparent feature of chondrodysplasia punctata (CDP), ichthyosis, Kallmann syndrome, or type 1 ocular albinism and those of their family members were investigated. High-resolution banding and FISH studies were performed using the probes of steroid sulfatase (STS), KAL1 and OA1, to detect the deleted status on Xp22.3 in these patients along with their mothers and/or sisters or maternal grandmothers.

RESULTS

All of these boys had normal karyotypes. FISH study showed nullisomy in 9 of the 23 male patients and hemizygosity in all female carriers in the genes on Xp22.3. The existence of 2 or more diseases in the same individual indicates a CGS. In addition, a putative mental retardation-related gene on Xp22.3 locus was considered to be located between X-linked CDP and STS.

CONCLUSIONS

The use of FISH probes for the Xp22.3 region allowed us to identify X-linked CGSs, especially in those patients with 2 or more distinct clinical entities or an obvious X-linked disorder.