Identification of a Novel Pathogenic ABCC6 Mutation Through Familial Genetic Analysis in Pseudoxanthoma Elasticum: A Case Report

通过家族遗传分析鉴定出一种新的致病性ABCC6突变,该突变与假性黄色瘤有关:病例报告

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Abstract

This study conducted genetic analysis on a patient clinically diagnosed with pseudoxanthoma elasticum (PXE) and their family to identify pathogenic mutations in the ABCC6 gene and analyze its inheritance pattern. We performed whole-exome sequencing of the ABCC6 gene on peripheral blood samples from the proband, his parents, and his sister, with validation via Sanger sequencing. Results revealed two heterozygous mutations in the proband: a previously reported missense mutation c.3412C>T (p. Arg1138Trp) and an unreported frameshift deletion mutation c.3160_3161del (p. Thr1054Glyfs*2). Both variants were classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. The c.3160_3161del mutation represents a novel pathogenic variant. The proband's mother carried the c.3412C>T mutation, while the father and sister carried the c.3160_3161del mutation. Among four family members, only the proband has been diagnosed with elastic fibrillary pseudoxanthoma. This pattern aligns with the typical autosomal recessive inheritance of PXE, with the proband being compound heterozygous. The findings of this study not only expand the spectrum of pathogenic mutations in the ABCC6 gene but also provide clear molecular evidence for genetic counselling and prenatal diagnosis.

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