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Nance-Horan syndrome (NHS) is a rare X-linked disorder characterized by congenital cataracts, dental anomalies and mental retardation. The disease has been linked to a novel gene termed NHS located at Xp22.13. The majority of pathogenic mutations of the disease include nonsense mutations and small deletions and insertions that lead to truncation of the NHS protein. In this study, we identified a microdeletion of ∼0.92 Mb at Xp22.13 detected by array-based comparative genomic hybridization in two brothers presenting congenital cataract, dental anomalies, facial dysmorphisms and mental retardation. The deleted region encompasses the REPS2, NHS, SCML1 and RAI2 genes, and was transmitted from their carrier mother who presented only mild cataract. Our findings are in line with several recent case reports to indicate that genomic rearrangement involving the NHS gene is an important genetic etiology underlying NHS. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase (CYP21) gene. More than 90% of CAH cases are caused by mutations of the CYP21 gene. Approximately 75% of the defective CYP21 genes are generated through intergenic recombination, termed "apparent gene conversion," from the neighboring CYP21Ppseudogene. A chimeric CYP21P/CYP21gene with its 5' end corresponding to CYP21P and 3' end corresponding to CYP21 has been identified. This type of gene is nonfunctional because it produces a truncated protein. We found two distinct chimeric genes in CAH patients. Both genes had a sequence with -300 nucleotides of the 5' head as the CYP21P gene. The coding region consisted of a fusion molecule with the CYP21P gene in two different regions. One of the junctions was located in the chi-like sequence of GCTGGGC in the third intron and the other was in the minisatellite consensus TGGCAGGAGG of exon 5 of the CYP21P gene. In addition, analysis of restriction fragment length polymorphism for these two 3.3-kb chimeric molecules showed that these sequences arose as a consequence of unequal crossover between the CYP21Pand CYP21 genes. It is plausible that both consensus sequences are responsible for the gene conversion of these two chimeric genes.