Functional and genetic studies have identified association between several Zinc finger (ZNF) proteins and Parkinson's disease (PD). However, most of them were still awaiting further replications, especially in the Asian population. Here, we systematically selected PD-relevant ZNF genes and analyzed the genetic associations between these ZNFs and PD in a large Chinese PD cohort. We identified rare variants (minor allele frequency < 0.01) in 743 unrelated patients with early-onset PD (EOPD, age at onset < 50 years) using whole exome sequencing and evaluated the association between rare variants and EOPD at both allele and gene levels. Totally 91 rare variants were identified in ZNF746, ZNF646, ZNF184, ZNF165, ZND219, and GLIS1. One variant p.R373H in ZNF219 and two variants p.G161D and p.R158H in ZNF746 were significantly associated with EOPD, and gene-based burden analysis showed enrichment of rare variants of ZNF746 in EOPD. Our findings build up the connection between ZNF746 and PD from a genetic perspective for the first time, supplement current understanding for the genetic role of ZNFs in EOPD, and broaden the mutation spectrum in PD.
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http://dx.doi.org/10.1007/s12035-021-02354-5 | DOI Listing |
Nat Commun
December 2024
Center for Health and Data Science (CHDS), the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Limited whole genome sequencing (WGS) studies in Asian populations result in a lack of representative reference panels, thus hindering the discovery of ancestry-specific variants. Here, we present the South and East Asian reference Database (SEAD) panel ( https://imputationserver.westlake.
View Article and Find Full Text PDFAnn Clin Transl Neurol
December 2024
Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P. R. China.
Background: Variants in the GABRA2 gene, which encodes the α2 subunit of the γ-aminobutyric acid A receptor, have been linked to a rare form of developmental and epileptic encephalopathy (DEE) referred to as DEE78. Only eight patients have been reported globally. This study presents the clinical presentation and genetic analysis of a Chinese family with a child diagnosed with DEE78, due to a novel GABRA2 variant.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Innovation Center for Diagnostics and Treatment of Thalassemia, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Despite the well-documented mutation spectra of β-thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long-read sequencing (T-LRS) is demonstrated to capture 20 genes/loci in 1,020 β-thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci.
View Article and Find Full Text PDFJ Pediatr Hematol Oncol
January 2025
Medical Faculty, University of Belgrade.
Nijmegen breakage syndrome (NBS) is a rare primary immunodeficiency disease due to a pathogenic variant in the NBN gene causing impaired DNA repair and increased predisposition for lymphoid malignancy. By contrast, solid tumors have been rarely reported. Neuroblastoma (NB) is a rare childhood solid tumor, associated with the worse outcome if MYCN oncogene is amplified.
View Article and Find Full Text PDFCureus
November 2024
Physical Medicine and Rehabilitation, St. John's National Academy of Health Sciences, Bengaluru, IND.
Emery-Dreifuss Muscular Dystrophy (EDMD) is a rare genetic disorder characterized by muscle weakness, joint contractures, and cardiac dysfunction. Within this spectrum, EDMD Type 2, attributed to a heterozygous missense variant in exon 9 of the LMNA gene, presents a distinctive clinical profile. This case report details the presentation and management of a teenage girl displaying neck, trunk, upper and lower limb weakness, Achilles tendon contracture, and lordosis.
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