Abstract
BackgroundCopy-neutral absence of heterozygosity (CN-AOH) observed on a single chromosome or part of a chromosome may be indicative of uniparental disomy (UPD) and may require additional testing when such chromosomes or chromosome regions are known to harbor imprinted genes.Case presentationHere we report 2 cases of neonates that presented to clinic with hypotonia, poor oral skills including inability to feed by mouth, weak cry, no response to noxious stimulation and vertical plantar creases (case 1) and hypotonia and respiratory distress (case 2). A preliminary chromosome analysis showed normal karyotypes in both cases while the high-resolution single nucleotide polymorphism (SNP) microarray showed copy neutral absence of heterozygosity involving chromosome 15 distal long arm. In case 1, the CN-AOH involved a 28.7 Mb block from genomic coordinates 73703619_102429049. In case 2, the CN-AOH involved a 15.3 Mb block from genomic coordinates 54729197_70057534. In both cases, methylation-specific PCR did not detect an unmethylated allele for the SNRPN gene suggesting either a deletion of paternal allele or maternal UPD for chromosome 15. Since microarray analysis did not show any copy number alterations on chromosome 15, a microdeletion was ruled out.ConclusionsBased on our cases, we suggest that CN-AOH on chromosome 15, even if it does not involve the critical region of 15q12q13, should warrant additional studies for diagnosis of Prader–Willi/Angelman syndromes.
Highlights
Copy-neutral absence of heterozygosity (CN-AOH) observed on a single chromosome or part of a chromosome may be indicative of uniparental disomy (UPD) and may require additional testing when such chromosomes or chromosome regions are known to harbor imprinted genes.Case presentation: Here we report 2 cases of neonates that presented to clinic with hypotonia, poor oral skills including inability to feed by mouth, weak cry, no response to noxious stimulation and vertical plantar creases and hypotonia and respiratory distress
Based on our cases, we suggest that CN-AOH on chromosome 15, even if it does not involve the critical region of 15q12q13, should warrant additional studies for diagnosis of Prader–Willi/Angelman syndromes
Given that the single nucleotide polymorphism (SNP) microarray showed loss of heterozygosity (LOH)/AOH for chromosome 15 with normal gene dosage in both cases, these findings are consistent with maternal UPD 15 resulting in Prader–Willi syndrome in our patients
Summary
Copy-neutral absence of heterozygosity (CN-AOH) observed on a single chromosome or part of a chromosome may be indicative of uniparental disomy (UPD) and may require additional testing when such chromosomes or chromosome regions are known to harbor imprinted genes.Case presentation: Here we report 2 cases of neonates that presented to clinic with hypotonia, poor oral skills including inability to feed by mouth, weak cry, no response to noxious stimulation and vertical plantar creases (case 1) and hypotonia and respiratory distress (case 2). Advent of chromosome microarray (CMA) technology, especially using the oligonucleotide probes, has revolutionized the diagnosis of copy number variation (CNV) in various conditions such as developmental delay, congenital anomalies and dysmorphic features [1]. One of these CMA platforms with the single nucleotide polymorphism (SNP)-based microarray technology that facilitates detection of CNV, and genotype information at numerous polymorphic loci throughout the human genome. Analysis of SNP allele patterns from these SNP-based arrays cannot only confirm the CNV calls, and can detect regions of homozygosity [2] Due to this unique ability, SNP-based microarray analysis is becoming a more widely used diagnostic approach in many clinical laboratories [3, 4]. Regions of homozygosity observed using these SNP-based arrays are described using multiple terms such as loss of heterozygosity (LOH), absence of heterozygosity (AOH), runs of homozygosity (ROH) or long-contiguous stretch of homozygosity (LCSH) [2].
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