Genetic and genomic analysis of classic XXXX in Saudi Arabia.

@entity1 @entity34337 @entity72989 @entity12325 @entity231 @entity20195 @entity4188 @entity6716 @entity1492 @entity2070 @entity72990 @entity6484 @entity66503 @entity17967
PURPOSE: To determine the genetic and genomic alterations underlying classic @entity6716 in Saudi Arabia, a region with social preference for consanguineous marriage. METHODS: Prospective study of consecutive @entity1 referred to a pediatric ophthalmologist in Saudi Arabia (2005-2009). All @entity1 had @entity6484 ( @entity6484 ) analysis (sequencing and multiplex ligation-dependent probe amplification analysis if sequencing was normal). If @entity6484 analysis was negative, the following were performed: candidate gene sequencing ( @entity17967 [ @entity17967 ], @entity20195 [ @entity20195 ], @entity12325 , subfamily B [ @entity4188 ], paired-like homeodomain transcription factor 3 [ @entity66503 ], and v-maf avian musculoaponeurotic @entity1492 oncogene homolog [MAF]) and molecular karyotyping by array competitive genomic hybridization (250K single nucleotide polymorphism (SNP) arrays). RESULTS: All 12 probands (4 months-25 years of age; four @entity1 and eight @entity1 ) had @entity231 and @entity2070 in addition to no grossly visible iris. Four cases were familial. All cases were products of consanguineous unions except for three, one of which was endogamous. Heterozygous @entity6484 mutations (including two novel mutations) were detectable in all but two cases, both of which were sporadic. In one of these two cases, the phenotype segregated with homozygosity for a previously-reported pathogenic missense @entity17967 variant ( @entity34337 ) when homozygosity for chromosome 11q24.2 deletion (chr11:125,001,547-125,215,177 [ @entity72989 ; @entity72990 ]) was also present. In the other, no genetic or genomic abnormalities were found. CONCLUSIONS: The classic @entity6716 phenotype in Saudi Arabia is typically caused by heterozygous @entity6484 mutations, even in the setting of enhanced homozygosity from recent shared parental ancestry. For @entity6484 -negative cases, interaction between missense variation in an anterior segment developmental gene and copy number variation elsewhere in the genome may be a potential mechanism for the phenotype.
