Four novel mutations in the <i>GCH1</i> gene of Chinese patients with dopa‐responsive dystonia

Cao, Li; Zheng, Lan; Tang, Weiguo; Xiao, Qiang; Zhang, Ting; Tang, Huidong; He, Shan; Wang, Xijin; Ding, Jianqing; Chen, Shengdi

doi:10.1002/mds.22646

Cited by 31 publications

(29 citation statements)

References 32 publications

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“…Indeed, as indicated in the results, even if the mutant allele presents novel potential donor splice sites with increased consensus splicing value, the natural site only presents a moderately decreased consensus splicing value and is likely partially used, as previously reported [Kaler et al, 1994;McConville et al, 1996;Møller et al, 2000;Clavero et al, 2004;Cao et al, 2010]. Thus, the haploinsufficiency in this patient would be partial.…”

Section: Discussionmentioning

confidence: 50%

Report of two novel mutations in PTHLH associated with brachydactyly type E and literature review

Thomas‐Teinturier

Pereda

Garin

et al. 2015

American J of Med Genetics Pt A

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Autosomal-dominant brachydactyly type E is a congenital limb malformation characterized by small hands and feet as a result of shortened metacarpals and metatarsals. Alterations that predict haploinsufficiency of PTHLH, the gene coding for parathyroid hormone related protein (PTHrP), have been identified as a cause of this disorder in seven families. Here, we report three patients affected with brachydactyly type E, caused by PTHLH mutations expected to result in haploinsufficiency, and discuss our data compared to published reports.

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Section: Discussionmentioning

confidence: 50%

Report of two novel mutations in PTHLH associated with brachydactyly type E and literature review

Thomas‐Teinturier

Pereda

Garin

et al. 2015

American J of Med Genetics Pt A

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“…The exon-intron boundaries are special regions that usually have important functional roles in proteins. 10 Indeed, NNSplice predicts that variant c. 453 þ 6 G4T affects the acceptor score of the splice site. We speculate that L145F and c. 453 þ 6G4T interact synergistically in the pathogenesis of case B.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12][13] All patients in this analysis met the diagnosis criteria for DRD. 14 Each mutation was classified as a (1) missense mutation; (2) exon-intron boundary variant, that is, a variant located in an exon-intron boundary region; (3) large deletion,which can be deleted only by multiple ligation-dependent probe amplification analysis; or (4) small deletion, which can be detected only by direct sequencing.…”

Section: Genotype-phenotype Correlationmentioning

confidence: 99%

“…[9][10][11][12][13] To extent these studies to China and increase the clinical value of phenotype-genotype analysis of DRD patients, in the present study, we screened GCH1 mutations in two families containing members newly diagnosed with DRD. We also conducted phenotype-genotype correlation analysis on the largest cohort of Chinese DRD patients to date, comprising all patients previously reported.…”

Section: Introductionmentioning

confidence: 99%

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Two novel mutations of the GTP cyclohydrolase 1 gene and genotype–phenotype correlation in Chinese Dopa-responsive dystonia patients

Zhou

et al. 2012

Eur J Hum Genet

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The most common form of Dopa-responsive dystonia (DRD) is caused by heterozygous mutations in the GTP cyclohydrolase I (GCH1) gene. We screened two unrelated, DRD-symptomatic Chinese Han individuals, for GCH1 gene mutations by direct sequencing. As the clinical manifestations of DRD are highly variable, we also explored the association between genotype and phenotype in all Chinese DRD patients reported so far in the literature, comprising 62 DRD-affected patients from 36 Chinese families. Two novel missense mutations (T94M, L145F) and a novel variant (c. 453 þ 6 G4T) were identified in our two new patients. None of these variants was detected in 200 healthy controls. On the basis of this and other reports, heterozygous mutations were detected in 90.3% of Chinese Han subjects with DRD. Seeming the age of onset for males and females, the mean age was 13 years older in males than in females (P ¼ 0.006). Different mutation types did not show any significant differences in age of onset, gender composition, initial symptoms, or the L-dopa dose that abolished the symptoms. Among DRD patients lacking missense or exon-intron boundary mutations, 68.4% were found to possess a large deletion in GCH1, which were detected by multiplex ligation-dependent probe amplification. Most GCH1 mutations were found to cluster in two regions of the coding sequence, suggesting the probable existence of mutation hotspot for the first time. The genotype-phenotype correlation described here may improve our understanding of DRD in Chinese individuals.

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“…Relatedly, RBD in PD or LBD is associated with a lower Braak stage and independently predicts the development of hallucinations (Arnulf, 2013; Dugger et al, 2012). In the early stages of PD 20 to 45% of patients report fleeting sideway shadows (‘passage’ hallucinations) or a sensation of presence (Fénelon, Soulas, Cleret de Langavant, Trinkler, & Bachoud-Levi, 2011; Fénelon, Soulas, Zenasni, & de Langavant, 2010; Mack et al, 2012). Pareidolias and visual hallucinations are common in patients with LBD (Uchiyama et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Altered functional connectivity in lesional peduncular hallucinosis with REM sleep behavior disorder

Geddes

Tie

Gabrieli

et al. 2016

Cortex

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Brainstem lesions causing peduncular hallucinosis (PH) produce vivid visual hallucinations occasionally accompanied by sleep disorders. Overlapping brainstem regions modulate visual pathways and REM sleep functions via gating of thalamocortical networks. A 66-year-old man with paroxysmal atrial fibrillation developed abrupt-onset complex visual hallucinations with preserved insight and violent dream enactment behavior. Brain MRI showed restricted diffusion in the left rostrodorsal pons suggestive of an acute ischemic infarct. REM sleep behavior disorder (RBD) was diagnosed on polysomnography. We investigated the integrity of ponto-geniculate-occipital circuits with seed-based resting-state functional connectivity MRI (rs-fcMRI) in this patient compared to 46 controls. Rs-fcMRI revealed significantly reduced functional connectivity between the lesion and lateral geniculate nuclei (LGN), and between LGN and visual association cortex compared to controls. Conversely, functional connectivity between brainstem and visual association cortex, and between visual association cortex and PFC was significantly increased in the patient. Focal damage to the left rostrodorsal pons is sufficient to cause RBD and PH in humans, suggesting an overlapping mechanism in both syndromes. This lesion produced a pattern of altered functional connectivity consistent with disrupted visual cortex connectivity via de-afferentation of thalamocortical pathways.

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Four novel mutations in the GCH1 gene of Chinese patients with dopa‐responsive dystonia

Cited by 31 publications

References 32 publications

Report of two novel mutations in PTHLH associated with brachydactyly type E and literature review

Report of two novel mutations in PTHLH associated with brachydactyly type E and literature review

Two novel mutations of the GTP cyclohydrolase 1 gene and genotype–phenotype correlation in Chinese Dopa-responsive dystonia patients

Altered functional connectivity in lesional peduncular hallucinosis with REM sleep behavior disorder

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