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Ataxia With Vitamin E Deficiency: Case Series, Vitamin E Therapy Response, Founder Effect, and in Silico Analysis Publisher Pubmed



Biglari S1, 2 ; Nikuei P3, 4 ; Mir A5 ; Vahidnezhad H2 ; Youssefian L6 ; Moghaddam AS7 ; Tabatabaiefar MA1 ; Saeidian AH2, 8 ; Khorram E1, 9 ; Fard MAF10 ; Farbood Z11 ; Shahrooei M12, 13 ; Khorshid HRK14 ; Esmaeilzadeh E15
Authors

Source: Clinical Genetics Published:2025


Abstract

Ataxia with Vitamin E Deficiency (AVED) is a rare autosomal recessive genetic disorder, that caused by pathogenic variants in the TTPA gene, which encodes the alpha-tocopherol transfer protein. This study investigates eight patients from three consanguineous Iranian families, using exome sequencing (ES) and Sanger sequencing to identify novel pathogenic variants in the TTPA gene. Two variants were identified: c.219T>A (p.Tyr73*) and c.205-1G>C. the first one (c.219T>A) related to potentially founder effects within regions of homozygosity. Clinical outcomes varied among patients based on vitamin E therapy initiation, with early treatment preventing severe neurological impairment. These findings improve knowledge of TTPA variants, supporting targeted genetic-based therapy. This study emphasizes the importance of genetic screening in consanguineous communities for the early detection and management of Mendelian diseases, with additional implications for managing rare genetic disorders generally. © 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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