Dopa-Responsive Dystonia in Han Chinese Patients: One Novel Heterozygous Mutation in GTP Cyclohydrolase 1 (GCH1) and Three Known Mutations in TH

Yang, Kunfang; Yin, Rongrong; Lan, Xiaoping; Zhang, Yuanfeng; Cheng, Han; Wang, Simei; Wang, Chunmei; Lu, Yanfen; Xi, Jiaming; Lü, Qin; Huang, Jian; Chen, Yucai

doi:10.12659/msm.907288

Cited by 6 publications

(8 citation statements)

References 21 publications

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“…We performed a literature search to clarify whether patients from different geographical regions carrying the R233H mutation and those harboring a heterozygous R233H mutation also displayed similar genotype-phenotype correlations. Therefore, we analyzed reports of 42 eligible patients, which was a sufficient number of cases to support this analysis [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Our analysis revealed that the homozygous R233H mutation frequently manifests as Type A TH deficiency, whereas R233H/nonsense mutation frequently manifests as Type B TH deficiency.…”

Section: Discussionmentioning

confidence: 96%

“…We analyzed the clinical manifestations, diagnosis, and treatment of the 4 patients diagnosed with TH deficiency at Beijing Tiantan Hospital (Table 1, Ref. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]), . To obtain data on all patients with R233H mutation in TH deficiency reported to date, we searched Medline, PubMed, China National Knowledge Infrastructure (ht tp://www.cnki.net), and Wanfang Data (http://www.wanf angdata.com.cn) databases for papers published in English or Chinese up to August 2020.…”

Section: Methodsmentioning

confidence: 99%

“…Among all 42 patients, there were 19 males and 14 females, and 9 for which gender was unknown (Table 1, Ref. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]). There were 22 patients with Type A TH deficiency, 17 patients with severe Type B TH deficiency, and the phenotype of remaining 2 patients was not clear.…”

Section: Clinical Data Of Patients With Th Deficiency From Our Hospital and The Ones From Literaturementioning

confidence: 99%

“…In recent years, TH deficiency has been diag-nosed with increasing frequency. Direct mutation analysis has been performed in more than 100 TH deficiency patients, and R233H is the most frequent mutation, with 21 patients of 53 from China and 21 patients from the remaining other countries carrying this mutation [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. This mutation is a G to A transversion at amino-acid position 698, resulting in histidine instead of arginine within the highly conserved domain of the TH protein, that is thought to interfere with the normal functioning of the TH protein.…”

Section: Introductionmentioning

confidence: 99%

“…A total of 42 patients with a mutation in R233H could be analyzed, including 21 patients from China (Table 1, Ref. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]). Meanwhile, in this study, we reviewed the clinical features, treatment, and prognosis of four patients with homozygous mutation of R233H in TH at our hospital.…”

Section: Introductionmentioning

confidence: 99%

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R233H mutation in patients with tyrosine hydroxylase deficiency and corresponding phenotypes: a study of four cases and literature review

Yao¹,

Deng²,

Wang³

et al. 2022

J. Integr. Neurosci.

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Owing to the small number of patients with tyrosine hydroxylase (TH) deficiency, no genotype-phenotype correlations have yet been identified. To investigate the genotype-phenotype correlation of R233H mutation in TH deficiency, we analyzed the clinical manifestations and treatment responses of four patients with the R233H homozygous mutation. Thirty-eight additional patients, available from the literature, known to be homozygous or heterozygous for the R233H mutation, were combined with the four cases from our hospital. Data for a total of 42 patients were retrieved. Our four patients showed clinical presentation consistent with Type A TH deficiency, and responded well to levodopa therapy, with an improvement in clinical symptoms within 1-2 weeks. In the 42 patients, 20 of 42 patients (48%) were homozygous and 22 (52%) were heterozygous for the R233H mutation. Of the 20 patients who were homozygous for the R233H mutation, a majority (80%) su fered from Type A TH deficiency. Of the 8 patients that were heterozygous for the R233H/the mutation located downstream of exon 11, 7 patients (86%) su fered from Type B TH deficiency. Of the 7 patients who were heterozygous for the R233H/nonsense mutation, 6 (86%) su fered from Type B TH deficiency. Genotype-phenotype correlation of R233H mutation was observed in TH deficiency. The homozygous R233H mutation frequently manifests as Type A TH deficiency, whereas R233H/nonsense mutation or any mutation located downstream of exon 11 manifests as Type B TH deficiency.

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Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Clinical Data Of Patients With Th Deficiency From Our Hospital and The Ones From Literaturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

R233H mutation in patients with tyrosine hydroxylase deficiency and corresponding phenotypes: a study of four cases and literature review

Yao¹,

Deng²,

Wang³

et al. 2022

J. Integr. Neurosci.

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Two heterozygous mutations in the calcium/calmodulin‐dependent serine protein kinase gene (CASK) in cases with developmental disorders

Yang

Lin

Fang

et al. 2022

Molec Gen & Gen Med

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Background:The calcium/calmodulin-dependent serine protein kinase gene (CASK) is an essential gene in mammals, critical for neurodevelopment. The purpose of this study is to expand the understanding of the diagnosis of CASK-linked disorders. Materials/Methods: From clinical and genetic mutational analyses, relevant data in 2 Han Chinese patients were collected and analyzed. Real-time quantitative PCR (RT-qPCR) was performed to investigate the CASK expression levels in the patients. The X-chromosome inactivation (XCI) patterns of the patients and their nuclear families were tested by quantitation of methylation of the polymorphic human androgen receptor (HUMARA) locus. Results: Two Han Chinese patients both presented with intellectual disability (ID), microcephaly with pontine and cerebellar hypoplasia (MICPCH). Two de novo mutations of c.82C>T (p.Arg28*) and c.846C>G (p.Tyr282*) in CASK have been investigated and predicted to be deleterious, which have produced truncated proteins. The functional protein association network of STRING (http:// strin g-db.org) generated three-dimensional (3D) atomic models based on protein sequences in CASK and two Arg28 and Tyr282 residues were marked. RT-qPCR showed lower copy numbers of CASK expression in the patients than in their parents, as well as the sex-and age-matched control groups. Patient 1 showed a skewed XCI pattern, while no related changes noted in patient 2. Conclusions: Patients carrying different nonsense variants may have different degrees of different clinical phenotypes. This study expands the spectrum of genotype and phenotype correlations of CASK-linked disorders in the Han Chinese ethnicity and provides new insights into the molecular mechanism.

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Dopa-responsive dystonia caused by tyrosine hydroxylase deficiency

et al. 2020

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Rational: Tyrosine hydroxylase deficiency (THD) is a rare cause of dopa-responsive dystonia (DRD). Although the symptoms of DRD may be improved by treatment with L-dopa, the low morbidity of THD can lead to its misdiagnosis. Thus, it is important for physicians to be aware of THD as a cause of DRD. Patient concerns: We report 3 cases of THD. A 5-year-old boy with DRD was diagnosed with THD and found to have compound heterozygous mutations of the TH gene, including TH:c.647G>C from his mother and TH:c.646G>A from his father. Two female siblings also were found to have TH:c.698G>A from their mother and TH:c.710T>C from their father. The younger daughter, at age 3.5 years, was diagnosed with DRD caused by THD, and then the diagnosis of the older daughter, at age 11 years, was changed from cerebral palsy to DRD caused by THD. Diagnosis: The diagnosis of dopa-responsive dystonia caused by tyrosine hydroxylase deficiency was determined by whole exome sequencing. Intervention: They all treated with low dose levodopa and benserazide tablets. Outcomes: The boy had a very good therapeutic effect, and he could walk very well by the second day of treatment. The younger sister of the siblings had a partial therapeutic effect, but her elder sister was only little effective with a milder improvement of dystonia and improvement of myodynamia. Conclusion: The characteristics of THD are heterogeneous, and its phenotypes are classified as type A or type B according to increasing severity. Generally, L-dopa has a good therapeutic effect in cases with type A phenotypes. We reviewed 87 cases of reported in the literature and found that c.698G>A and c.707T>C are hot spot mutations. Changes on cerebral magnetic resonance imaging were nonspecific. Analysis of neurotransmitter levels in cerebrospinal fluid is an invasive means of achieving a biochemical diagnosis.

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Dopa-Responsive Dystonia in Han Chinese Patients: One Novel Heterozygous Mutation in GTP Cyclohydrolase 1 (GCH1) and Three Known Mutations in TH

Cited by 6 publications

References 21 publications

R233H mutation in patients with tyrosine hydroxylase deficiency and corresponding phenotypes: a study of four cases and literature review

R233H mutation in patients with tyrosine hydroxylase deficiency and corresponding phenotypes: a study of four cases and literature review

Two heterozygous mutations in the calcium/calmodulin‐dependent serine protein kinase gene (CASK) in cases with developmental disorders

Dopa-responsive dystonia caused by tyrosine hydroxylase deficiency

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