ClinVar Genomic variation as it relates to human health

Using PCR-SSCP analysis and direct DNA sequencing, van den Hurk et al. (1992) detected and characterized different mutations in the CHM gene in 5 patients with choroideremia (CHM; 303100). Patient 2086 had a 4-bp deletion (delTGTT) in exon 'C,' causing a frameshift predicted to result in premature termination at codon 198. Van den Hurk et al. (1997) referred to this mutation as 1614_1617delTGTT in exon 13. In a Danish patient with choroideremia, Schwartz et al. (1993) identified the same 4-bp deletion in exon 'C' of the CHM gene. Noting that this deletion was identical to that found by van den Hurk et al. (1992) in a German family with choroideremia, Schwartz et al. (1993) suggested that it may represent a mutational hotspot that is susceptible to slippage during replication since the TGTT sequence is duplicated in the normal sequence position. In a 3-generation French family with choroideremia, consisting of 3 affected males, 5 carrier females, and 1 unaffected male, Pascal et al. (1993) analyzed 5 exons of the CHM gene and identified the same 4-bp deletion. In a 21-year-old Chinese man with retinal degeneration that was initially diagnosed as retinitis pigmentosa (see 268000), Li et al. (2014) identified the recurrent 4-bp deletion, which they designated c.1584_1587delTGTT, in exon 13 of the CHM gene. Review of fundus images showed changes consistent with choroideremia. The patient had an affected maternal uncle. Examination of the proband's obligate carrier mother, who had normal visual acuity without night blindness, revealed a number of yellow crystalline-like spots in the macular area and irregular mottled pigmentation in the midperiphery. Electroretinography showed normal rod responses and mildly reduced cone responses. (less)