Combined whole exome sequencing and chromosomal microarray analysis improve clinical interpretation of genomic variants in patients with intellectual disability

Introduction aCGH determines pathogenic copy number variations (CNVs) in about 10% of patients with intellectual disability (ID). In another 20% patients, probably CNVs or variants uncertain clinical significance are detected. It may be that do not fully explain the patient’s symptoms, aberrations reduced penetrance inherited from healthy parents. The use a sequencing method for such cases is advisable. Objectives Improvement diagnosis disability. Methods 60K Agilent microarrays, qPCR, targeted sequencing, whole exome (WES). Results Six ID and deletions/duplications detected by their parents if available were further examined sequencing. Four had maternal CNVs: (1) del1q41 ( SPATA17, LINC00210, RRP15 ), (2) del7q35 TCAF2 , exon 8), (3) dup8p22p21.3 PSD3, exons 1-11), (4) del12p11.1 SYT10, 1-2). Two paternal (5) dup1q44 SMYD3 2-5) (6) del15q11.2 TUBGCP5, CYFIP1, NIPA1, NIPA2, LOC283683 ). severe phenotype patient could explained paternally disruption single gene. WES determined SNV MID1 gene associated Opitz GBBB syndrome (OMIM 300000), which corresponds better to likely cause disease. Although included region chromosome 1q41-q42 deletion 612530) much milder; two MPO, MAN2C1 ) one ARID1B SNVs. pat additional 7 ARSE SNVs KIDINS220, FOXG1 genes. No del7q35. For SYT10 revealed no as well. Conclusions Sometimes aCGH-analysis sufficient identify causes ID, however, case detection and/or parents, it necessary examine using methods. So, accurate was made eight. combination SNPs should considered. last three described genome solution.This study supported Russian Science Foundation, grant 21-65-00017, https://rscf.ru/project/21-65-00017/ Disclosure Interest None Declared