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In a study of 43 ALS patients of North-African Jewish origin, rare homozygous in‑silico damaging variants were assessed, and CFAP54 (HGNC:26456) emerged as a candidate gene based on its altered expression profile. A truncating variant, c.1852A>T (p.Lys618Ter), was reported in one proband under an autosomal recessive model, suggesting a potential but limited contribution of CFAP54 to amyotrophic lateral sclerosis (PMID:31108397). The genetic evidence is further constrained by the lack of extensive segregation data and additional multi‑family support, as only a single variant event is currently documented. Moreover, while CFAP54 has been implicated in other conditions through functional studies, no experimental assays have established its pathogenic mechanism in ALS. This limited gene‑disease evidence underscores the need for larger cohorts and targeted familial analyses to better clarify its role in the disease. As such, the current findings provide only a modest basis for clinical diagnostic use in ALS.
Functional data specific to ALS remain absent for CFAP54, with reported experimental studies instead validating its role in primary ciliary dyskinesia and male infertility. Consequently, despite the autosomal recessive pattern observed in the genetic study, the functional evidence does not support a direct mechanistic link between CFAP54 and ALS. Additional investigation, including robust segregation studies and targeted functional assessments in neuronal models, is required to enhance confidence in this association. Overall, while CFAP54 represents a plausible candidate gene, its current clinical utility in ALS diagnostics is limited. Key take‑home: CFAP54 should be considered a tentative candidate in ALS, warranting further genetic and experimental validation before routine clinical application.
Gene–Disease AssociationLimitedA single truncating variant (c.1852A>T (p.Lys618Ter)) was identified in one ALS proband with no additional segregation data (PMID:31108397), limiting the overall gene‑disease association. Genetic EvidenceLimitedOnly one autosomal recessive truncating variant in CFAP54 was reported from a multi‑patient study, with insufficient segregation or recurrence data to support a stronger genetic claim (PMID:31108397). Functional EvidenceNoneNo functional experiments have validated the role of CFAP54 in ALS; available studies focus on its involvement in primary ciliary dyskinesia and male infertility. |