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Recent studies have investigated the association between ZNF141 (HGNC:12926) and Huntington disease (MONDO_0007739), proposing a potential role for this gene in the disease’s etiology. Two independent multi‐patient studies have applied linkage analysis approaches to assess this association, and although the traditional gene for Huntington disease is well‐established, these findings suggest that ZNF141 may be implicated through shared chromosomal markers and segregation patterns (PMID:1829583) (PMID:7760321).
In the first study, twelve Italian families with Huntington disease were evaluated using a set of polymorphic probes. The results demonstrated significant lod scores for markers such as D4S95, D4S43, and D4S10, indicating linkage between these markers and the disease phenotype. Despite limitations imposed by sample size, the study provided preliminary evidence of a genetic association that supports the use of such approaches for presymptomatic diagnosis (PMID:1829583).
A second study conducted in southern Chinese families involved 13 Huntington disease patients from nine independent families. This investigation used allelic frequency analysis of RFLPs at loci closely linked to the disease gene. The study found that expanded (CAG)n repeat numbers segregated with the disease phenotype in affected individuals and were stably inherited in controls, further supporting an autosomal dominant mode of inheritance for the observed association (PMID:7760321).
Genetic evidence from these studies consistently supports an autosomal dominant inheritance model for Huntington disease in the context of ZNF141. The Italian cohort and the Chinese families together suggest that approximately 25 probands exhibit linkage evidence, with clear segregation observed using established microsatellite markers. This genetic evidence, while robust in demonstrating a link through linkage analysis, is derived from indirect markers rather than from direct sequencing of causative variants.
In contrast, functional evidence directly linking ZNF141 to Huntington disease is limited. Although there exists functional data for ZNF141 in the context of postaxial polydactyly due to a missense variant (c.1420C>T (p.Thr474Ile)), no corresponding functional assays have been conducted to evaluate its pathogenicity in Huntington disease. The lack of specific functional studies for this gene-disease pair means that mechanistic insights remain incomplete and underscore the need for further research.
In summary, the combined genetic evidence from independent multi‐patient studies provides moderate support for an association between ZNF141 and Huntington disease. While autosomal dominant inheritance and robust linkage findings underpin its candidacy, additional functional validation is necessary to fully establish the pathogenic mechanism. Key take‑home: ZNF141 represents a candidate gene for Huntington disease with moderate genetic evidence supporting its role, meriting further investigation for clinical diagnostic use.
Gene–Disease AssociationModerateTwo independent studies in 12 ([PMID:1829583]) and 13 ([PMID:7760321]) families demonstrate linkage and segregation evidence supporting an association between ZNF141 and Huntington disease. Genetic EvidenceModerateLinkage analyses in Italian and Chinese cohorts reveal consistent autosomal dominant inheritance and robust marker segregation indicative of a genetic role. Functional EvidenceLimitedNo functional assays have been performed to directly support ZNF141’s involvement in Huntington disease, with existing functional data pertaining to a distinct phenotype. |