Ethnic Differences in Dystonia Prevalence and Phenotype

Mulroy, Eoin; Macerollo, Antonella; Scotton, S.; Cociasu, Ioana; Lazzaro, Giulia Di; Bashir, Shaima; Doherty, John A.; Hamid, Shahd; Mooney, Nicole; Batla, Amit; Morgante, Francesca; Bhatia, Kailash P.

doi:10.1002/mds.29034

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…Previous studies have shed light on the differences in the phenotypic profile of dystonia across various ethnicities. 38 The study by Almasy et al 39 in the mid-nineties expanded the outlook on ethnic differences beyond the conventional knowledge of greater affliction of idiopathic torsion dystonia among the Ashkenazi Jews. Their important observation of the phenotypic difference between the Jewish and non-Jewish dystonia cohorts paved the way for further research.…”

Section: Asian Cohort Of Patients With Kmt2b-related Disordersmentioning

confidence: 99%

KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort

Dhar¹,

Holla²,

Kumari³

et al. 2023

JMD

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ObjectiveaaMutations in the KMT2B gene have been identified in patients previously diagnosed with idiopathic dystonia. Literature on KMT2B-related dystonia is sparse in the Indian and Asian populations.MethodsaaWe report seven patients with KMT2B-related dystonia studied prospectively from May 2021 to September 2022. Patients underwent deep clinical phenotyping and genetic testing by whole-exome sequencing (WES). A systematic literature search was performed to identify the spectrum of previously published KMT2B-related disorders in the Asian subcontinent.ResultsaaThe seven identified patients with KMT2B-related dystonia had a median age at onset of four years. The majority experienced onset in the lower limbs (n = 5, 71.4%), with generalization at a median duration of 2 years. All patients except one had complex phenotypes manifesting as facial dysmorphism (n = 4), microcephaly (n = 3), developmental delay (n = 3), and short stature (n = 1). Magnetic resonance imaging (MRI) abnormalities were present in four cases. WES revealed novel mutations in the KMT2B gene in all patients except one. Compared to the largest cohort of patients with KMT2B-related disorders, the Asian cohort, comprising 42 patients, had a lower prevalence of female patients, facial dysmorphism, microcephaly, intellectual disability, and MRI abnormalities. Protein-truncating variants were more prevalent than missense variants. While microcephaly and short stature were more common in patients with missense mutations, facial dysmorphism was more common in patients with truncating variants. Deep brain stimulation, performed in 17 patients, had satisfactory outcomes.ConclusionaaThis is the largest series of patients with KMT2B-related disorders from India, further expanding the clinico-genotypic spectrum. The extended Asian cohort emphasizes the unique attributes of this part of the world.

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Section: Asian Cohort Of Patients With Kmt2b-related Disordersmentioning

confidence: 99%

KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort

Dhar¹,

Holla²,

Kumari³

et al. 2023

JMD

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“…Moreover, patients with isolated dystonia in different ethnic populations may have varying clinical phenotypes. 6 A systemic analysis of the genetic and phenotypic features of patients with isolated dystonia in the Chinese population is still lacking.…”

Section: Introductionmentioning

confidence: 99%

“…However, due to the low incidence, only some studies of WES have been performed on Chinese patients with isolated dystonia. Moreover, patients with isolated dystonia in different ethnic populations may have varying clinical phenotypes 6 . A systemic analysis of the genetic and phenotypic features of patients with isolated dystonia in the Chinese population is still lacking.…”

Section: Introductionmentioning

confidence: 99%

Genetic spectrum and clinical features in a cohort of Chinese patients with isolated dystonia

Liu

Huang

et al. 2023

Clinical Genetics

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Dystonia is a genetically and phenotypically heterogeneous disorder that occurs in isolation (isolated dystonia) or in combination with other movement disorders. To determine the genetic spectrum in isolated dystonia, we enrolled 88 patients with isolated dystonia for whole-exome sequencing (WES). Seventeen mutations, including nine novel ones, were identified in 19 of the 88 patients, providing a 21.59% positive molecular diagnostic rate. Eleven distinct genes were involved, of which TOR1A and THAP1 accounted for 47.37% (9/19) of the positive cases. A novel missense variant, p.S225R in TOR1A, was found in a patient with adolescence-onset generalized dystonia. Cellular experiments revealed that p.S255R results in the abnormal aggregation of Torsin-1A encoding by TOR1A. In addition, we reviewed the clinical and genetic features of the isolated dystonia patients carrying TOR1A, THAP1, ANO3, and GNAL mutations in the Chinese population. Our results expand the genetic spectrum and clinical profiles of patients with isolated dystonia and demonstrate WES as an effective strategy for the molecular diagnosis of isolated dystonia.

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What can epidemiological studies teach on the pathophysiology of adult-onset isolated dystonia?

Martino¹

2023

International Review of Neurobiology

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Ethnic Differences in Dystonia Prevalence and Phenotype

Cited by 5 publications

References 14 publications

KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort

KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort

Genetic spectrum and clinical features in a cohort of Chinese patients with isolated dystonia

What can epidemiological studies teach on the pathophysiology of adult-onset isolated dystonia?

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