Tremor Ataxia With Central Hypomyelation Phenotype Related to a Recurrent POLR3A Mutation in Six Unrelated Tunisian Families.

Autor: Kraoua I; LR18SP04, Department of Child and Adolescent Neurology, Faculty of Medicine of Tunis, National Institute Mongi Ben Hmida of Neurology, University of Tunis El Manar, Tunis, Tunisia., Jamoussi M; LR18SP04, Department of Child and Adolescent Neurology, Faculty of Medicine of Tunis, National Institute Mongi Ben Hmida of Neurology, University of Tunis El Manar, Tunis, Tunisia., Drissi C; Department of Neuroradiology, Faculty of Medicine of Tunis, National Institute Mongi Ben Hmida of Neurology, University of Tunis El Manar, Tunis, Tunisia., Kraoua L; Department of Congenital and Hereditary Diseases, Faculty of Medicine of Tunis, Charles Nicolle Hospital, University of Tunis El Manar, Tunis, Tunisia., Drunat S; Génétique Moléculaire, DMU BioGeM, APHP, Hôpital Robert Debré, Paris, France.; INSERM UMR1141, Hôpital Robert Debré, Université Paris Cité, Paris, France., Benrhouma H; LR18SP04, Department of Child and Adolescent Neurology, Faculty of Medicine of Tunis, National Institute Mongi Ben Hmida of Neurology, University of Tunis El Manar, Tunis, Tunisia., Ben Younes T; LR18SP04, Department of Child and Adolescent Neurology, Faculty of Medicine of Tunis, National Institute Mongi Ben Hmida of Neurology, University of Tunis El Manar, Tunis, Tunisia., Nagi S; Department of Neuroradiology, Faculty of Medicine of Tunis, National Institute Mongi Ben Hmida of Neurology, University of Tunis El Manar, Tunis, Tunisia., Abdelhak S; LR11IPT05, Laboratory of Biomedical Genomics and Oncogenetics, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia., Boespflug Tanguy O; INSERM UMR1141, Hôpital Robert Debré, Université Paris Cité, Paris, France.; Service de Neuropédiatrie, Centre de Reference LEUKOFRANCE, APHP, Hôpital Robert Debré, Paris, France., Youssef-Turki IB; LR18SP04, Department of Child and Adolescent Neurology, Faculty of Medicine of Tunis, National Institute Mongi Ben Hmida of Neurology, University of Tunis El Manar, Tunis, Tunisia., Trabelsi M; Department of Congenital and Hereditary Diseases, Faculty of Medicine of Tunis, Charles Nicolle Hospital, University of Tunis El Manar, Tunis, Tunisia., Dorboz I; INSERM UMR1141, Hôpital Robert Debré, Université Paris Cité, Paris, France.; Service de Neuropédiatrie, Centre de Reference LEUKOFRANCE, APHP, Hôpital Robert Debré, Paris, France.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2024 Oct; Vol. 12 (10), pp. e70007.
DOI: 10.1002/mgg3.70007
Abstrakt: 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.
(© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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