Chromosomal microarray in a highly consanguineous population: diagnostic yield, utility of regions of homozygosity, and novel mutations.
Clin Genet
; 91(4): 616-622, 2017 Apr.
Article
em En
| MEDLINE
| ID: mdl-27717089
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aberrações Cromossômicas
/
Análise de Sequência com Séries de Oligonucleotídeos
/
Variações do Número de Cópias de DNA
/
Doenças Genéticas Inatas
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article