Screening and analysis of genetic pathogenesis in children with intellectual disorder
Objective To analyze the genetic etiology of children with intellectual developmental disorders(ID),and to provide a basis for clinical diagnosis and treatment of ID diseases and genetic counseling of family lines.Methods 5 cases of children with ID diagnosed in the First Affiliated Hospital of Xi'an Jiaotong University from January 2020 to January 2021 were selected for the study.Preliminary classification of the 5 children with ID was carried out by karyotype analysis,and whole exome sequencing analysis was performed in the children with normal chromosome analysis results,and the possible pathogenic variants screened by whole exome sequencing were verified and functionally analyzed by Sanger sequencing and bioinformatics analysis software.Results The karyotype analysis revealed that P1 children had a karyotype of 46,XY,del(18)(q22q23),and the remaining four children had normal karyotypes.Whole exome sequencing results showed that 2 children had compound heterozygous variants of c.2096G＞A(p.Ser699Asn)and c.2644_2655del(p.Ser882_Gly885del)in the ATP2C2 gene.Family validation showed that the mothers of P2 and P3 children were carriers of the heterozygous variant of the ATP2C2 gene c.2096G＞A(p.Ser699Asn)and the fathers were carriers of the heterozygous variant of the ATP2C2 gene c.2644_2655del(p.Ser882_Gly885del).The heterozygous variant of the ATP2C2 gene c.2096G＞A(p.Ser699Asn)variant locus was not found in databases such as Shenzhou Genome Data 1000 Genome,ExAC and gnomAD.The amino acids encoded by the bioinformatically analyzed variants(c.2096G＞A and c.2644_2655del)are highly conserved across species and both could lead to altered protein structure.Conclusion The ATP2C2 genes c.2096G＞A(p.Ser699Asn)and c.2644_2655del(p.Ser882_Gly885del)are newly identified variant loci that may be causative of ID.
万方数据
维普
