Disease-causing deletions/amplifications may include a single gene, several exons or single/part of exon, contributing to detection of novel pathogenic genes. The localization of single-gene deletion/amplification within the gene can affect its clinical manifestation.

Improvement of diagnosis of intellectual disability.

aCGH with 60K Agilent microarrays, qPCR.

Among 1099 patients with intellectual disability potentially pathogenic single-gene deletions/amplifications were detected in 51 individuals (5%). qPCR was used to verify aberrations in 21 patients (41%). Ten mutations were of maternal origin, four - paternal, two - de novo, another two were confirmed without analysis of parents, and three could not be confirmed. Single-gene aberrations involving the AGBL4 (exon 2), ASMT (exon 9), CYP2C18 (whole gene), DDX10 (promoter, exons 1-13), GYPA (whole gene), LIG4 (exon 1), LSAMP (intron 1), PSD3 (promoter, exons 1-11), SNTB1 (intron 1), SPOCK3 (exons 6-12), STAG2 (exons 7-34), SYT10 (promoter, exons 1-2), TCAF2 (exon 8), TMPRSS15 (promoter, exons 1-12), and ZDHHC7 (promoter, exons 1-4) genes were described by us for the first time. Deletion or amplification of several exons within a gene can affect transcription as point mutation does, while the copy number change of a whole gene can lead to an abnormal amount of the protein.

Fifteen novel genes potentially responsible for mental health were identified. In most of them aberrations were partial deletions/duplications. Most of abnormalities were inherited from healthy parents indicating the possible presence of a point mutation on the second allele or some modifying factors. This study was supported by the Russian Science Foundation, grant 21-65-00017.

No significant relationships.