Biallelic Truncating DNAH14 Variant in Siblings with Neurodevelopmental Disorder and Predominant Ataxia: Clinical Report and Literature Review

Baris S, Dogan M, Terali K, Gezdirici A, Eroz R, Yucel PP, Kilic H, Yavas C, Yildirim G, Baris I. Biallelic Truncating DNAH14 Variant in Siblings with Neurodevelopmental Disorder and Predominant Ataxia: Clinical Report and Literature Review. Int J Mol Sci. 2026 Jan 6;27(2):575. doi: 10.3390/ijms27020575. PMID: 41596228; PMCID: PMC12841059.

The coexistence of FRDA expansions and a truncating DNAH14 variant suggests a potential dual genetic contribution to the observed phenotype, in which FRDA-associated pathology likely underlies the ataxia, while DNAH14 disruption may contribute to additional neurodevelopmental features. This is the first report describing the co-occurrence of FRDA and a homozygous truncating DNAH14 variant in the same individuals, broadening our understanding of overlapping neurogenetic mechanisms. Our findings expand the phenotypic spectrum of DNAH14-related disorders and highlight the importance of considering multilocus pathogenic variants in patients with complex or atypical ataxia presentations.

Hereditary Ataxias: From Pathogenesis and Clinical Features to Neuroimaging, Fluid, and Digital Biomarkers-A Scoping Review

Bernardi E, López-Lombardía Ó, Olmedo-Saura G, Pagonabarraga J, Kulisevsky J, Pérez-Pérez J. Hereditary Ataxias: From Pathogenesis and Clinical Features to Neuroimaging, Fluid, and Digital Biomarkers-A Scoping Review. Int J Mol Sci. 2026 Jan 15;27(2):881. doi: 10.3390/ijms27020881. PMID: 41596528; PMCID: PMC12841259.

We conducted a scoping review of PubMed and complementary sources (2010-2025) to map and describe the current landscape of genetic, imaging, fluid, electrophysiological, and digital biomarkers across the most prevalent hereditary ataxias, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, SCA27B, dentatorubral-pallidoluysian atrophy (DRPLA), Friedreich's ataxia (FRDA), RFC1-related ataxia (CANVAS), SPG7, and fragile X-associated tremor/ataxia syndrome (FXTAS). 

 Mapping current approaches also reveals substantial variability and gaps across diseases and modalities, underscoring the need for harmonized validation in international multicenter cohorts and systematic integration into future clinical trials to advance precision medicine in hereditary ataxias.

Quantifying Placebo Effects in Hereditary Ataxia Trials: A Meta-Analysis of Scale for the Assessment and Rating of Ataxia (SARA) Score Changes

Petit E, Beaubois-Gandoin A, Durr A, du Montcel ST, Coarelli G. Quantifying Placebo Effects in Hereditary Ataxia Trials: A Meta-Analysis of Scale for the Assessment and Rating of Ataxia (SARA) Score Changes. Mov Disord. 2026 Jan 29. doi: 10.1002/mds.70151. Epub ahead of print. PMID: 41612637. 

 The analysis indicates a measurable placebo effect on SARA scores. Both intervention type and geographic region significantly influenced the strength of this effect, suggesting roles for patient expectations and cultural factors. Additionally, there was a trend toward reduction of placebo response as trial duration increased.