Enter Note Done


Keywords: Development; Intellectual and developmental disability; Genome sequencing; X-linked disease; Copy number/structural variation

W. He 1; T. Chiang 1; J. Shen 1; X. Wang 2; H. Wang 2; Y. Yang 1; X. Wang 1

1) AiLife Diagnostics, Pearland, TX.; 2) Sichuan Provincial Maternal and Child Health Hospital, Chengdu, China

Low-pass WGS has recently been reported to be able to detect CNVs at the resolution comparable with that of chromosomal microarray analysis (CMA). In the meantime, the coverage of CMA is variable across the genome depending on the probes included in the assay, low-pass WGS has much more uniformed coverage and can potentially detect CNVs encompassing any genes. While low-pass WGS has been shown to effectively detect large CNVs, its utility in detecting smaller events is relatively unknown. Here we report the identification of a single exon deletion in RPS6KA3 gene by low-pass WGS in a male patient with global developmental delay, hypertelorism, hearing impairment, and hypotonia. At the mean coverage of 3X (paired end reads), WGS detected the hemizygous deletion encompassing exon 1 of RPS6KA3. The size of the deletion is about ~42 kb (chrX:20257168-20299113, hg19). RPS6KA3 is associated with X-linked Coffin-Lowry syndrome [MIM: 303600] or mental retardation X-linked 19 [MIM: 300844]. Coffin-Lowry syndrome typically present with dysmorphic facial features including hypertelorism, sensorineural hearing loss, skeletal abnormalities, hypotonia, and neurologic problems, which are consistent with the clinical features of this patient. Interestingly whole exome sequencing (WES) was ordered concurrently for this patient. CNV analysis based on the WES depth of coverage revealed no reads aligned to exon 1 of RPS6KA3 in this patient, consistent with the WGS findings. Our results showed that low-pass WGS, which is usually used to detected gross deletions and duplications, can also detect smaller, intra-genic CNVs.