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.

Pathological frataxin deficiency in mice causes tissue-specific alterations in iron homeostasis

Pazos-Gil M, Medina-Carbonero M, Sanz-Alcázar A, Portillo-Carrasquer M, Oliveira-Jorge L, Hernández G, Sánchez M, Delaspre F, Cabiscol E, Ros J, Tamarit J. Pathological frataxin deficiency in mice causes tissue-specific alterations in iron homeostasis. iScience. 2026 Jan 5;29(2):114625. doi: 10.1016/j.isci.2025.114625. PMID: 41623463; PMCID: PMC12857413.

In this study, we have analyzed iron homeostasis in a mouse model presenting pathological frataxin deficiency (FXNI151F). Our results reveal tissue-specific alterations of iron regulatory proteins (IRPs).

Friedreich-Ataxie: Die häufigste autosomal-rezessiv vererbte Ataxie [Friedreich's ataxia: The most common autosomal recessive inherited ataxia]

Erdlenbruch F. Friedreich-Ataxie: Die häufigste autosomal-rezessiv vererbte Ataxie [Friedreich's ataxia: The most common autosomal recessive inherited ataxia]. MMW Fortschr Med. 2026 Feb;168(Suppl 1):40-42. German. doi: 10.1007/s15006-026-5619-2. PMID: 41699226.

Die Friedreich-Ataxie ist eine seltene, autosomal-rezessiv vererbte, (neuro)degenerative Multisystemerkrankung. Neben dem Nervensystem sind auch das Herz, der Bewegungsapparat und der Stoffwechsel beeinträchtigt. Die Krankheit bricht i. d. R. im Jugendalter aus. …

Coexistence of Friedreich's Ataxia and Esophageal Cancer: A Case Report

Mehrban A, Babamahmoodi A, Hamidian MT, Amiri B, Ramzani P, Karimi M. Coexistence of Friedreich's Ataxia and Esophageal Cancer: A Case Report. Clin Case Rep. 2026 Feb 24;14(3):e72153. doi: 10.1002/ccr3.72153. PMID: 41756699; PMCID: PMC12932118.

Friedreich's ataxia (FA) is a rare autosomal recessive neurodegenerative disorder. Although FA is frequently associated with cardiomyopathy and diabetes mellitus, its coexistence with solid malignancies is exceptionally rare. To date, only a limited number of gastrointestinal cancers have been reported in patients with FA.

Therapeutic Potential of Deferiprone-Resveratrol Hybrid (DFP-RVT) Against Hepatic Iron Overload in β-Thalassemia Mice: A Proteomic Analysis

Maneekesorn S, Yingchutrakul Y, Simanon N, Kumsab J, Butkinaree C, Moonmuang S, Li J, Charoenkwan P, Koonyosying P, Paradee N, Srichairatanakool S, Chuljerm H. Therapeutic Potential of Deferiprone-Resveratrol Hybrid (DFP-RVT) Against Hepatic Iron Overload in β-Thalassemia Mice: A Proteomic Analysis. Biomolecules. 2026 Feb 23;16(2):338. doi: 10.3390/biom16020338. PMID: 41750406; PMCID: PMC12937802. 

Proteomic analysis was performed on liver tissues from baseline control, iron-overloaded, and DFP-RVT-treated mice to identify differentially expressed proteins and affected pathways. Iron overload resulted in marked downregulation of mitochondrial proteins, particularly components of oxidative phosphorylation and iron-sulfur cluster-associated pathways, including frataxin.

Our findings suggest that frataxin may be a key determinant of mitochondrial integrity and function in the context of hepatic iron overload. The observed frataxin loss in IO mice, likely driven by iron toxicity, contributes to hepatocellular damage. Importantly, DFP-RVT treatment restored frataxin expression, which may account for the recovery of mitochondrial protein levels and overall mitochondrial function

Dimethyl fumarate and mitochondrial physiology: implications for neurological disorders

de Oliveira MR. Dimethyl fumarate and mitochondrial physiology: implications for neurological disorders. Front Pharmacol. 2026 Feb 12;17:1748360. doi: 10.3389/fphar.2026.1748360. PMID: 41769702; PMCID: PMC12935978.

In conclusion, DMF exerts multifaceted and cell type-specific actions on mitochondria. Understanding these mechanisms may guide optimized therapeutic strategies and the identification of biomarkers for precision use in neurological disorders.

An Exploration of Vitamin D Deficiency and Clinical Status in Friedreich's Ataxia Patients in the UK

Fleszar Z, Thomas-Black G, Garcia-Moreno H, Cook A, Giunti P. An Exploration of Vitamin D Deficiency and Clinical Status in Friedreich's Ataxia Patients in the UK. Mov Disord Clin Pract. 2026 Mar 6. doi: 10.1002/mdc3.70529. Epub ahead of print. PMID: 41789678. 

Given the established benefits for bone health, particularly in a cohort in which falls are highly prevalent, coupled with the low cost and good safety profile of supplementation, we recommend that vitamin D deficiency should be screened for and actively managed in all FRDA patients.

Identification of Biological Subtypes of Friedreich Ataxia with Structural MRI-based Machine Learning

Pontillo G, Penna S, Arrigoni F, Bender B, Boesch S, Brunetti A, Cendes F, Chopra S, Corben LA, Deistung A, Delatycki MB, Diciotti S, Dogan I, Egan GF, França MC Jr, Georgiou-Karistianis N, Göricke SL, Henry PG, Hernandez-Castillo CR, Hutter D, Joers JM, Lenglet C, Lindig T, Lodi R, Manners DN, Martinez ARM, Martinuzzi A, Marzi C, Mascalchi M, Nachbauer W, Pane C, Peruzzo D, Pishardy PK, Reetz K, Rezende TJR, Romanzetti S, Saccà F, Schoels L, Schulz JB, Stefani A, Synofzik M, Thomopoulos SI, Thompson PM, Timmann D, Tonon C, Vavla M, Harding IH, Cocozza S. Identification of Biological Subtypes of Friedreich Ataxia with Structural MRI-based Machine Learning. Radiology. 2026 Mar;318(3):e251386. doi: 10.1148/radiol.251386. PMID: 41805414. 

Using the SuStaIn algorithm, three distinct structural MRI-based subtypes of FRDA were identified, with different patterns of brain degeneration and associations with clinical severity