title: Chromosomal microarray in a highly consanguineous population: diagnostic yield, utility of regions of homozygosity, and novel mutations.
abstract: 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.
authors.affiliation: Pediatrics Department, Tawam Hospital, Al-Ain, United Arab Emirates.
authors.forename: M A
authors.initials: MA
authors.lastname: Alabdullatif
authors.affiliation: Pediatrics Department, Tawam Hospital, Al-Ain, United Arab Emirates.
authors.forename: M A
authors.initials: MA
authors.lastname: Al Dhaibani
authors.affiliation: Pediatrics Department, Tawam Hospital, Al-Ain, United Arab Emirates.|Pediatric Department, Jordan University of Science and Technology, Jordan.
authors.forename: M Y
authors.initials: MY
authors.lastname: Khassawneh
authors.affiliation: Division of Clinical Genetics and Metabolic Disorders, Tawam Hospital, Al-Ain, United Arab Emirates.
authors.forename: A W
authors.initials: AW
authors.lastname: El-Hattab
mesh_terms: D002675:Child, Preschool; D002869:Chromosome Aberrations; D003241:Consanguinity; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D030342:Genetic Diseases, Inborn / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
keywords: autosomal recessive diseases; chromosomal microarray; consanguinity; novel gene mutations; regions of homozygosity