Genetic analysis of a family with Shashi-Pena syndrome
Objective To analyze the clinical data of family with Shashi-Pena syndrome,to explore the genetic etiology,and to provide genetic counseling and prenatal diagnosis for this family.Methods A child with Shashi-Pena syndrome was diagnosed and treated in Henan Provincial People's Hospital in April,2022.The clinical data of her family were collected.The peripheral blood of the proband and her parents were collected for G-banding analysis and whole exome sequencing.The candidate pathogenic variation was analyzed by bioinformatics software,and the Ex AC,1000Genomes and gnomeAD database were searched for comparison of mutated loci.The pathogenic variation was verified by Sanger sequencing.The conservation of variation in 7 species(human,chimpanzee,rhesus monkey,wolf,cow,mouse and rat)was analyzed by UCSC software.Swiss-Model software was used to analyze the protein structure.The pathogenicity of the variation was rated according to the guidelines of the American College of Medical Genetics and Genomics.The amniotic fluid of the mother was harvested.The prenatal diagnosis was performed for the fetal genetic testing and chromosome karyotype.The neonate was followed up for 6 months after birth.Results The proband had phenotypes of intellectual disability,delayed language development,movement disorders,macrocephaly and special facial features.The proband had ASXL2 gene c.1230delA(p.Lys410Asnfs*13)heterozygous mutation,and the loci of proband's parents were wild-type,which was the firstly reported de novo mutation.The 410th amino acid encoded by ASXL2 gene in seven species(human,chimpanzee,rhesus monkey,wolf,cow,mouse and rat)was highly conserved.The c.1230delA mutation of ASXL2 gene was a frameshift mutation,which led to the structural change of ASXL2 protein.The mutation was not recorded in the ExAC,1000Genomes or gnome AD databases,and was pathogenic mutation rated by ACMG.Based on the clinical manifestations,genetic features,gene sequencing and pathogenicity analysis,the patient was diagnosed with Shashi-Pena syndrome caused by ASXL2 gene mutation.The fetus carried no ASXL2 gene c.1230delA mutation.She was followed up for 6 months and there was no obvious growth abnormality.Conclusion The heterozygous mutation of the ASXL2 gene c.1230delA(p.Lys410Asnfs*13)is the pathogenic cause of Shashi-Pena syndrome in this family,which contributes to the genetic counseling for the parents and prenatal diagnosis for the fetus.
NETL
NSTL
万方数据
