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Case practice of variant re-evaluation and fertility consultation in cortical dysplasia associated with other brain malformations

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Author:
No author available
Journal Title:
Chinese Journal of Prenatal Diagnosis(Electronic Version)
Issue:
2
DOI:
10.13470/j.cnki.cjpd.2024.02.005
Key Word:
皮质发育不良伴其他脑畸形Ⅰ型;TUBB3基因;cortical dysplasia;TUBB3;brain malformations

Abstract: Objective To provide reproductive counseling and guidance for a pregnant woman who previously had a child with comprehensive developmental delays.Methods The proband has undergone a child development assessment,brain MRI scan,and whole-exome sequencing for the family.Based on the AC MG/AMP variant classification guidelines and supplementary recommendations from ClinGen,the proband's genetic report was re-evaluated.Results Whole-exome sequencing of the family identified a novel variant of uncertain significance in the TUBB3 gene(NM_006086.4),c.86G>A(p.Gly29Asp).After re-evaluating the pathogenicity of the variant,it was classified as likely pathogenic.This variant has not been previously reported in the literature.Considering the clinical phenotype,variant pathogenicity,pathogenic mechanism,inheritance pattern,and after a multidisciplinary team consultation,the proband was considered to have cortical dysplasia with other brain malformations type I.Conclusion Re-evaluating genetic reports with unclear clinical significance can improve diagnostic yield and provide valuable guidance for reproductive counseling.

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