Molecular genetics & genomic medicine · 2024
Tremor Ataxia With Central Hypomyelation Phenotype Related to a Recurrent POLR3A Mutation in Six Unrelated Tunisian Families.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Kraoua Ichraf, Jamoussi Maha, Drissi Cyrine, Kraoua Lilia, Drunat Séverine, Benrhouma Hanene, Ben Younes Thouraya, Nagi Sonia, Abdelhak Sonia, Boespflug Tanguy Odile, Youssef-Turki Ilhem Ben, Trabelsi Mediha, Dorboz Imen
Аннотация
BACKGROUND: POLIII-related leukodystrophies are a group of recently recognized hereditary white matter diseases with a similar clinical and radiological phenotype. No Tunisian studies have been published about POLIII-related leukodystrophy due to POLR3A variants. The aim of this study was to contribute to the clinical, radiological, and genetic characterization of POLR3A-related leukodystrophy in a Tunisian cohort.
METHODS: We report six cases of genetically confirmed POLR3A-related leukodystrophy belonging to six unrelated Tunisian families, along with a review of previously published pediatric cases.
RESULTS: All patients were born to consanguineous marriages and originated from the North or the Center of Tunisia. Age at onset varied between 15 months and 6 years. The clinical phenotype was similar in all patients with cerebellar ataxia, tremor, and nystagmus being the key features. Brain imaging showed diffuse hypomyelination in all patients with progressive cerebellar atrophy in three patients. Molecular analysis identified the same bi-allelic NM_007055.4:c.2011T>C; p.(Trp671Arg) variant in the POLR3A gene in all patients.
CONCLUSION: We hypothesize a founder effect for the identified variant given its recurrence in six unrelated individuals with a similar clinical phenotype. Given the apparent genetic homogeneity of Tunisian POLR3A patients, the recurrent variant should be directly targeted. This should facilitate diagnosis in index patients, and genetic counseling.
METHODS: We report six cases of genetically confirmed POLR3A-related leukodystrophy belonging to six unrelated Tunisian families, along with a review of previously published pediatric cases.
RESULTS: All patients were born to consanguineous marriages and originated from the North or the Center of Tunisia. Age at onset varied between 15 months and 6 years. The clinical phenotype was similar in all patients with cerebellar ataxia, tremor, and nystagmus being the key features. Brain imaging showed diffuse hypomyelination in all patients with progressive cerebellar atrophy in three patients. Molecular analysis identified the same bi-allelic NM_007055.4:c.2011T>C; p.(Trp671Arg) variant in the POLR3A gene in all patients.
CONCLUSION: We hypothesize a founder effect for the identified variant given its recurrence in six unrelated individuals with a similar clinical phenotype. Given the apparent genetic homogeneity of Tunisian POLR3A patients, the recurrent variant should be directly targeted. This should facilitate diagnosis in index patients, and genetic counseling.