scholarly journals Novel Mutation in CACNA1A Associated with Activity-Induced Dystonia, Cervical Dystonia, and Mild Ataxia

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Benjamin Stampfl ◽  
Dominic Fee
Keyword(s):  
Cervical Dystonia ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Cerebellar Atrophy ◽  
Familial Hemiplegic Migraine ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 6 ◽  
History Of ◽  
The Brain

CACNA1A encodes the pore-forming α1 subunit of the neuronal voltage-gated Cav2.1 (P/Q-type) channels, which are predominantly localized at the presynaptic terminals of the brain and cerebellar neurons and play an important role in controlling neurotransmitter release. Mutations in CACNA1A have been associated with several autosomal dominant neurologic disorders, including familial hemiplegic migraine type 1, episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6. A 37-year-old woman presented with a history of slowly progressive, activity-induced stiffness, and pain in her right leg since age 15 and cervical dystonia since age 20. She denied any right leg stiffness or pain at rest, but when she began to walk, her right foot turned in and her right leg stiffened up. She also had neck pain, stiffness, and spams. There was no family history of similar symptoms. On physical exam, her strength, tone, and reflexes were normal in all extremities at rest. There was mild head titubation and very mild past pointing on finger-to-nose testing. MRI of the brain and spinal cord was unremarkable. This patient’s clinical picture was felt to be most consistent with paroxysmal kinesigenic dyskinesia, as she has attacks of dystonia that are triggered by voluntary movement, last from a few seconds to a minute, and are relieved with rest. She was trialed on carbidopa/levodopa without improvement. A dystonia panel showed two potentially pathologic mutations, one in CACNA1A and the other in PNKP, along with a variant of unknown significance in ATP7B. The mutation in CACNA1A is C2324 G < A. It is heterozygous, autosomal dominant, and computer modeling suggests pathogenicity. This mutation has not been reported previously and is likely the cause of her paroxysmal dystonia; dystonia is sometimes seen during episodes of ataxia in EA2, and CACNA1A knockout mice exhibit dystonia and cerebellar atrophy. After receiving her genetic diagnosis, the patient was trialed on acetazolamide without improvement in her dystonia symptoms. This is the second case report of a patient with cervical dystonia and cerebellar ataxia associated with a mutation in CACNA1A.

Toluene-induced leukodystrophy from glue sniffing

2021 ◽  
pp. practneurol-2021-002942
Author(s):  
Yue Hui Lau ◽  
Ahmad Shahir Mawardi ◽  
Norzaini Rose Zain ◽  
Shanthi Viswanathan
Keyword(s):  
Basal Ganglia ◽  
Cognitive Decline ◽  
Early Recognition ◽  
Cerebellar Atrophy ◽  
Premature Mortality ◽  
History Of ◽  
The Brain

A 33-year-old man with a history of chronic toluene abuse through glue sniffing, developed tremors, cerebellar signs and cognitive decline. MR scan of the brain showed global cerebral and cerebellar atrophy with symmetrical T2-weighted hypointensities in the basal ganglia, thalami and midbrain. After stopping glue sniffing, his tremors, ataxia of gait, speech and cognition partially improved. Early recognition and intervention of toluene-induced leukodystrophy could prevent ongoing morbidity and premature mortality.

scholarly journals Mutations in NOTCH3 Gene may Promote the Clinical Presentation of Spinocerebellar Ataxia Type 37 Caused by Mutations in DAB1 Gene

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhao-Wei Wang ◽  
Li-Ping Wang ◽  
Ye Du ◽  
Qi Liu
Keyword(s):  
Spinocerebellar Ataxia ◽  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Bioinformatics Analysis ◽  
Clinical Presentation ◽  
Cerebellar Atrophy ◽  
Gene Mutations ◽  
Brain Magnetic Resonance Imaging ◽  
Diagnostic Methods ◽  
Spinocerebellar Ataxia Type

Background: Autosomal dominant spinocerebellar ataxia type 37 (SCA37) and Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) result from DAB1 and NOTCH3 gene mutations, respectively.Methods: In addition to conventional diagnostic methods, next-generation sequencing (NGS) and Sanger sequencing were performed to define and confirm the DAB1 and NOTCH3 gene mutation for a Chinese pedigree. Bioinformatics analysis was also applied for the mutated DAB1 and NOTCH3 protein using available software tools.Results: Brain magnetic resonance imaging shows diffuse leukoencephalopathy and cerebellar atrophy in the proband. NGS and Sanger sequencing identified two novel heterozygous mutations: NM_021080:c.318T &gt; G (p.H106Q) in the DAB1 gene and NM_000435:c.3298C &gt; T (p.R1100C) in the NOTCH3 gene. Bioinformatics analysis suggested that the DAB1 and NOTCH3 gene mutations are disease-causing and may be responsible for the phenotypes.Conclusion: This is the first report of a pedigree with both SAC37 and CADASIL phenotypes carrying corresponding gene mutations. Mutations in the NOTCH3 gene may promote the clinical presentation of spinocerebellar ataxia type 37 caused by mutations in the DAB1 gene. In addition to general examinations, it is vital for physicians to apply molecular genetics to get an accurate diagnosis in the clinic, especially for rare diseases.

scholarly journals Neuromyelitis Optica Spectrum Disorder Coinciding with Spinocerebellar Ataxia Type 31

2017 ◽  
Vol 9 (2) ◽  
pp. 127-130
Author(s):  
Yoshiaki Takahashi ◽  
Yasuhiro Manabe ◽  
Ryuta Morihara ◽  
Hisashi Narai ◽  
Toru Yamashita ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Neuromyelitis Optica ◽  
Cerebellar Atrophy ◽  
Spectrum Disorder ◽  
Spinocerebellar Ataxia Type ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Inflammatory Processes ◽  
Thoracic Cord ◽  
The Brain ◽  
Cerebellar Symptoms

We report the unusual case of a 63-year-old man with spinocerebellar ataxia (SCA) type 31 who developed neuromyelitis optica spectrum disorder (NMOSD) 14 years after the onset of cerebellar symptoms. In addition to cerebellar atrophy, magnetic resonance imaging showed multiple high-intensity areas in the brain and a long thoracic cord lesion from Th1/2 to Th11. The combination of NMOSD and SCA31 is accidental. However, our case suggests that inflammatory processes could be involved in the pathogenesis of NMOSD and SCA31.

scholarly journals A Novel Mutation in TSC2 Gene: A 34-Year-Old Female with Pulmonary Lymphangioleiomyomatosis with Concomitant Hepatic Lesions

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Mehdi Nadiri ◽  
Mortaza Raeisi ◽  
Seyed Ali Mousavi Aghdas
Keyword(s):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Reproductive Age ◽  
Response To Treatment ◽  
Tsc2 Gene ◽  
Pulmonary Lymphangioleiomyomatosis ◽  
Dominant Disease ◽  
Hepatic Lesions ◽  
The Impact ◽  
The Brain

Tuberous sclerosis complex (TSC) is an autosomal dominant disease resulting from mutation(s) in TSC1 or TSC2 genes. TSC is associated with the formation of hamartomas in the brain, heart, eyes, skin, kidneys, and lymphangioleiomyomatosis (LAM) of the lungs. LAM is almost restricted to women in reproductive age. Different mutations in TSC1 and TSC2 genes have been reported in the literature. Here, we present a female patient with TSC-LAM with a novel mutation in TSC2 gene. The patient also had multiple hepatic angiomyolipomas, which is a relatively less-reported manifestation of the disease. The impact of this mutation on the pattern of disease presentation and response to treatment is not clear yet.

scholarly journals A Novel Nonsense Mutation ofPOU4F3Gene Causes Autosomal Dominant Hearing Loss

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Chi Zhang ◽  
Mingming Wang ◽  
Yun Xiao ◽  
Fengguo Zhang ◽  
Yicui Zhou ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Nonsense Mutation ◽  
Autosomal Dominant ◽  
Late Onset ◽  
Stop Codon ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Chinese Family ◽  
Nonsyndromic Hearing Loss ◽  
Truncated Protein

POU4F3gene encodes a transcription factor which plays an essential role in the maturation and maintenance of hair cells in cochlea and vestibular system. Several mutations ofPOU4F3have been reported to cause autosomal dominant nonsyndromic hearing loss in recent years. In this study, we describe a pathogenic nonsense mutation located inPOU4F3in a four-generation Chinese family. Target region capture sequencing was performed to search for the candidate mutations from 81 genes related to nonsyndromic hearing loss in this family. A novel nonsense mutation ofPOU4F3, c.337C>T (p.Gln113⁎), was identified in a Chinese family characterized by late-onset progressive nonsyndromic hearing loss. The novel mutation cosegregated with hearing loss in this family and was absent in 200 ethnicity-matched controls. The mutation led to a stop codon and thus a truncated protein with no functional domains remained. Transient transfection and immunofluorescence assay revealed that the subcellular localization of the truncated protein differed markedly from normal protein, which could be the underlying reason for complete loss of its normal function. Here, we report the first nonsense mutation ofPOU4F3associated with progressive hearing loss and explored the possible underlying mechanism. Routine examination ofPOU4F3is necessary for the genetic diagnosis of hereditary hearing loss in the future.

scholarly journals Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin–neurophysin II gene

2011 ◽  
Vol 165 (1) ◽  
pp. 161-165 ◽  
Author(s):  
M de Fost ◽  
A S P van Trotsenburg ◽  
H M van Santen ◽  
E Endert ◽  
C van den Elzen ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Water Deprivation ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Resonance Imaging ◽  
Exon 2 ◽  
Hyperintense Signal ◽  
The Brain ◽  
Neurophysin Ii

BackgroundFamilial neurohypophyseal (central) diabetes insipidus (DI) is caused by mutations in the arginine vasopressin–neurophysin II (AVP–NPII) gene. The majority of cases is inherited in an autosomal dominant way. In this study, we present the clinical features of a mother and her son with autosomal dominant neurohypophyseal DI caused by a novel mutation.CaseA thirty-four-year-old woman and her three-year-old son were evaluated because of polyuria and polydipsia since the age of 1.5 years onwards. Both patients were subjected to a water deprivation test confirming the diagnosis of central DI. Magnetic resonance imaging of the brain of the mother showed a hypothalamus without apparent abnormalities and a relatively small neurohypophysis without a hyperintense signal. Mutation analysis showed a c.322G>T (p.?/p.Glu108X) in Exon 2 of the AVP–NPII gene in both mother and son.DiscussionThis study reports neurohypophyseal DI in a mother and her son due to a novel mutation in Exon 2 of the AVP–NPII gene. Clinical and pathophysiological aspects of this disease are shortly reviewed and discussed.

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