Frequent detection of parental consanguinity in children with developmental disorders by a combined CGH and SNP microarray

Abstract

BackgroundGenomic microarrays have been used as the first-tier cytogenetic diagnostic test for patients with developmental delay/intellectual disability, autism spectrum disorders and/or multiple congenital anomalies. The use of SNP arrays has revealed regions of homozygosity in the genome which can lead to identification of uniparental disomy and parental consanguinity in addition to copy number variations. Consanguinity is associated with an increased risk of birth defects and autosomal recessive disorders. However, the frequency of parental consanguinity in children with developmental disabilities is unknown, and consanguineous couples may not be identified during doctor’s visit or genetic counseling without microarray.ResultsWe studied 607 proband pediatric patients referred for developmental disorders using a 4 × 180 K array containing both CGH and SNP probes. Using 720, 360, 180, and 90 Mb as the expected sizes of homozygosity for an estimated coefficient of inbreeding (F) 1/4, 1/8, 1/16, 1/32, parental consanguinity was detected in 21cases (3.46%).ConclusionParental consanguinity is not uncommon in children with developmental problems in our study population, and can be identified by use of a combined CGH and SNP chromosome microarray. Identification of parental consanguinity in such cases can be important for further diagnostic testing.

The clinical benefit of array-based comparative genomic hybridization for detection of copy number variants in Czech children with intellectual disability and developmental delay

“…Using 180 K CGH + SNP microarray platform we detected 1.5% cases (8/542) with large stretches of cnnLOH > 5 Mb, in which we identified from tens to hundreds of genes related to autosomal recessive disorders. The presence of more than one LOH locus indicates the parental consanguinity which is typical for individuals from inbred populations [35,36]. Based on low incidence of consanguinity in the Czech Republic (~0.2%) (www.consang.net) [37] we suggest to use CGH + SNP microarray platforms for analysis in specific families when the parental consanguinity is reported in the preliminary genetic counselling.…”

ISPD gene homozygous deletion identified by SNP array confirms prenatal manifestation of Walker–Warburg syndrome

“…To detect possible parental consanguinity, the absence of heterozygosity (AOH) (uninterrupted homozygote blocs ! 3 Mb) [Fan et al, 2013] was calculated in all foetuses. Nevertheless, 1e2% of the AOH in foetuses F1, F2 and F3 did not suggest the likelihood of a direct biological relationship between the parents.…”

Institutional Protocol to Manage Consanguinity Detected by Genetic Testing in Pregnancy in a Minor

“…1,7 Incidental detection of parental consanguinity by SNP array in children with developmental or congenital anomalies has been demonstrated in the literature. 2,8 In case 1, SNP array was performed for multiple congenital anomalies. Unexpected detection of multiple long homozygosity stretches led to the discovery of paternal child sexual abuse.…”

“…Thus, clinicians have the ability to identify previously unrecognized chromosomal disorders and, incidentally, consanguineous parental relationships. 2 Genetic testing may suggest not only consanguinity between consenting adults, but can also suggest parental rape and child sexual abuse. 3 Clinicians have a duty to report cases of suspected or confirmed sexual abuse.…”