Clinical Implications of Chromosome 16 Copy Number Variation

Abstract

Chromosome 16 is one of the gene-rich chromosomes; however, approximately 10% of the chromosome 16 sequence is composed of segmental copies, which renders this chromosome instable and predisposes it to rearrangements via frequent nonallelic homologous recombination. Microarray technologies have enabled the analysis of copy number variations (CNV), which may be associated with the risk of developing complex diseases. Through comparative genomic hybridisation in 1,298 patients, we detected 18 cases with chromosome 16 CNV. We identified 2recurrent CNV regions, including 1 at 16p13.11 in 4 patients and another at 16p11.2 in 7 patients. We also detected atypical chromosome 16 rearrangements in 7 patients. Furthermore, we noted an increased frequency of co-occurring genomic changes, supporting the two-hit hypothesis to explain the phenotypic variability in the clinical presentation of CNV syndromes. Our findings can contribute to the creation of a chromosome 16 disease map based on regions that may be associated with disease development.

Analysis of copy number variations and possible candidate genes in spontaneous abortion by copy number variation sequencing

“…The chromosomal trisomy was most often detected in chromosome 16, this is consistent with prior studies ( 30 ). Chromosome 16 is gene-rich but unstable due to a 10% segmental copy sequence, making it prone to frequent non-allelic homologous recombination and gene rearrangements ( 34 ). Advanced maternal age is a widely recognized risk that increases the risk of chromosomal abnormalities and spontaneous miscarriage, with the incidence of chromosomal aneuploidy being higher in women over 35 years old ( 35 – 38 ).…”

16p11.2 Microduplication Syndrome with Increased Fluid in the Cisterna: Coincidence or Phenotype Extension?

“…Recently, differences in brain structure and some significant MRI findings of people with 16p11.2 microduplication syndrome were described. Deletions and duplications of the 16p11.2 locus have already been associated with changes in brain anatomy [ 25 , 26 ]. Within those diagnosed with a duplication, microcephaly, cerebral white matter or corpus callosum abnormalities and ventricular enlargement were also observed, but less frequently than speech articulation abnormalities, hypotonia, abnormal agility, sacral dimples and seizures or epilepsy [ 26 , 27 ].…”

“…It was also found that human-induced pluripotent stem cell-derived neurons from 16p11.2 duplication carriers display corresponding features with reduced size/dendrite length in neurons [ 3 ]. Furthermore, the reduced cortical surface area has been reported, and analyses of cortex anatomies revealed reduced cortical thickness in both 16p11.2 deletion and duplication carriers [ 26 ].…”

16p13.11 microdeletion/microduplication in fetuses: investigation of associated ultrasound phenotypes, genetic anomalies, and pregnancy outcome follow-up

“…The cause of phenotypic diversity in patients with 16p13.11 microdeletion is still unclear and detailed analysis is warranted [21]. 16p13.11 microduplication has been linked to autism and neuropsychiatric disorders, including schizophrenia, attention deficit hyperactivity disorder, and intellectual disability [11,[22][23][24][25]. In fact, the influence of 16p13.11 microduplication is not without controversy, and some studies have reported it as a rare benign variant [26].…”