RESUMO
Chromosomal microarray (CMA) has significantly improved diagnosing copy number variations (CNVs). Single nucleotide polymorphism (SNP) arrays confer additional utility in detecting regions of homozygosity (ROH). Investigating ROH for genes associated with recessive disorders for follow-up sequencing can aid in diagnosis. In this study, we performed a retrospective review of clinical and molecular data for 227 individuals from a highly consanguineous population who previously had a CMA. Pathogenic CNVs were identified in 32 (14%) cases; ROH suggesting uniparental disomy (UPD) in three (1%) cases, and an additional 25 (11%) individuals were diagnosed with recessive disorders caused by mutations in ROH candidate genes, thereby increasing the CMA diagnostic yield to 26%. Among the 25 individuals with recessive diseases, 18 had novel mutations in 16 genes (ASPM, SPINK5, QARS, MEGF10, SPATA7, GMPPA, ABCA4, SRD5A2, RPGRIP1L, MET, SLC12A6, ALDH1A3, TNFRSF11A, FLNB, PHGDH, and FKBP10) including five with phenotypic expansion.
