Abstract
Objective: This study aims to explore the clinical characteristics and genetic basis of a patient with unilateral ptosis and unilateral hearing impairment in pedigree analysis. Methods: The clinical data of the child and his father were collected. The genomic DNA of the patient and his relatives were extracted from their peripheral blood samples and subjected to trio-whole-exome sequencing (trio-WES) and copy number variation analysis. Sanger sequencing was used to verify the potential variant. Results: The sequencing analysis identified a heterozygous nonsense variant c.6431C > A (p.Ser2144*) in the ZNF462 gene (NM_021224.6) in the child and his father, whereas the locus in his asymptomatic mother, brother, and grandparents was found to be the wild type, which is an autosomal dominant inheritance. The new genetic variant has not been previously reported in the ClinVar and HGMD databases and the Genome Aggregation Database (gnomAD). Conclusion: This is the first incidence of Weiss–Kruszka syndrome relating to the nonsense variant in the ZNF462 gene in China. The finding from this study is novel in its expansion of the variant spectrum of the ZNF462 gene and clarifies the genetic etiology of the patient and his father.
Highlights
Weiss–Kruszka syndrome (WSKA, MIM: 618,619) is a multiple congenital anomaly syndrome
The same keywords were used in PubMed, and six publications were found containing cases of WSKA associated with the ZNF462 gene
The first reported case identified a new balanced translocation t (2; 9) (p24; q32), and the multiple phenotypes of this individual could be due to the disruption in the ZNF462 gene and ASXL2 gene as a consequence of chromosomal rearrangement (Ramocki et al, 2003; Talisetti et al, 2003; Kruszka et al, 2019); Weiss et al reported that the dysfunctional variants of ZNF462 gene were found in six patients from four families with significant deletions in two different regions of chromosome nine were detected in two patients from two unrelated families (Weiss et al, 2017)
Summary
The clinical data of the child and his father were collected. The genomic DNA of the patient and his relatives were extracted from their peripheral blood samples and subjected to trio-whole-exome sequencing (trio-WES) and copy number variation analysis.
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