Comparative analysis of the autismrelated variants between different autistic children in a family pedigree.
Mol Med Rep
; 24(4)2021 Oct.
Article
en En
| MEDLINE
| ID: mdl-34368859
ABSTRACT
The present study aimed to provide evidence for the genetic heterogeneity of familial autism spectrum disorder (ASD), which might help to improve our understanding of the complex polygenic basis of this disease. Wholeexome sequencing (WES) was performed on two autistic children in a family pedigree, and reasonable conditions were set for preliminarily screening variant annotations. Sanger sequencing was used to verify the preliminarily screened variants and to determine the possible sources. In addition, autismrelated genes were screened according to autism databases, and their variants were compared between two autistic children. The results showed that there were 21 genes respectively for autistic children â
£2 and â
£4, preliminarily screened from all variants based on the harmfulness (high) and quality (high or medium) of the variants, as well as the association between mutant genes and autism in human gene mutation database. Furthermore, candidate autismrelated genes were screened according to the evidence score of >4 in the Autism KnowledgeBase (AutismKB) database or ≥3 in the AutDB database. A total of 11 and 10 candidate autismrelated genes were identified in the autistic children â
£2 and â
£4, respectively. Candidate genes with an evidence score of >16 in AutismKB were credible autismrelated genes, which included LAMC3, JMJD1C and CACNA1H in child â
£2, as well as SCN1A, SETD5, CHD7 and KCNMA1 in child â
£4. Other than the c.G1499A mutation of SCN1A, which is known to be associated with Dravet syndrome, the specific missense variant loci of other six highly credible putative autismrelated genes were reported for the first time, to the best of the authors' knowledge, in the present study. These credible autismrelated variants were inherited not only from immediate family members but also from extended family members. In summary, the present study established a reasonable and feasible method for screening credible autismrelated genes from WES results, which by be worth extending into clinical practice. The different credible autismrelated genes between the two autistic children indicated a complex polygenic architecture of ASD, which may assist in the early diagnosis of this disease.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Linaje
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Trastorno Autístico
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Predisposición Genética a la Enfermedad
Tipo de estudio:
Prognostic_studies
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Screening_studies
Límite:
Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Mol Med Rep
Año:
2021
Tipo del documento:
Article