Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease

Liu, Yidan; Chu, Xu; Liu, Ruihua; Sun, Ying; Kong, Qingxia; Li, Qiubo

doi:10.3892/mmr.2019.10133

Cited by 4 publications

(4 citation statements)

References 32 publications

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“…Therefore, when the mutation is occurred, the E1β stability might be changed, leading to the MSUD. This was in the good agreement with the previous studies that the mutations occurred in exon 10 of the BCKDHB gene are associated closely with the pathogenesis of MSUD, for example,: mutation C382 (Imtiaz et al, 2017), mutation Y383 (Henneke et al., 2003), mutation R359 (Lui et al, 2019). Based on the phenotype presented here, we propose the P368 variant also to be contributing to the cause of MSUD.…”

Section: Discussionsupporting

confidence: 92%

“…Therefore, the K + position in the E1β structure of humans is very important for protein stability and function (Arnthor et al., 2000; Chuang, Wynn, Song, & Chuang, 1999). As reported by Lui et al (2019), the mutation that caused the deletion of a thymine at position 705 (c.705delT) in exon 6 was classified as a likely pathogenic agent (Lui et al, 2019).…”

Section: Discussionmentioning

confidence: 98%

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Identification of novel mutations in BCKDHB and DBT genes in Vietnamese patients with maple sirup urine disease

Nguyen

Nguyễn

et al. 2020

Molec Gen & Gen Med

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Background Maple sirup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder. The disease‐causing mutations can affect the BCKDHA , BCKDHB , and DBT genes encoding for the E1α, E1β, and E2 subunits of the multienzyme branched‐chain α‐keto acid dehydrogenase (BCKDH) complex. In the present study, novel pathogenic variants in BCKDHB and DBT genes were identified in three Vietnamese families with MSUD. Methods Three newborn patients from three unrelated Vietnamese families were diagnosed with MSUD at the Metabolic Clinic, National Hospital of Pediatrics. Blood samples of 11 relatives from two generations of the three families diagnosed with MSUD were analyzed using exome and Sanger sequencing analyses. Results Novel pathogenic variants in BCKDHB (c.1103C>T, c.989A>G, and c.704G>A), and DBT (c.263_265delAAG) genes were identified in three pediatric patients with MSUD. Conclusions We have identified novel pathogenic variants in the MSUD‐related genes in the pedigree of the three patient's families. Our findings expand the mutational spectrum of MSUD and provide the scientific basis for genetic counseling for the patient's families.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 98%

Identification of novel mutations in BCKDHB and DBT genes in Vietnamese patients with maple sirup urine disease

Nguyen

Nguyễn

et al. 2020

Molec Gen & Gen Med

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“…These siblings exhibited compound heterozygous mutations (c.1076G>A [p.Arg359Lys] and c.705delT [p.Cys235Ter]) in the BCKDHB gene (OMIM 248611). 113 …”

Section: Channelopathiesmentioning

confidence: 99%

Genetic Links to Episodic Movement Disorders: Current Insights

Garg¹,

Mohammad²,

Shukla³

et al. 2023

TACG

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Episodic or paroxysmal movement disorders (PxMD) are conditions, which occur episodically, are transient, usually have normal interictal periods, and are characterized by hyperkinetic disorders, including ataxia, chorea, dystonia, and ballism. Broadly, these comprise paroxysmal dyskinesias (paroxysmal kinesigenic and non-kinesigenic dyskinesia [PKD/PNKD], paroxysmal exercise-induced dyskinesias [PED]) and episodic ataxias (EA) types 1–9. Classification of paroxysmal dyskinesias has traditionally been clinical. However, with advancement in genetics and the discovery of the molecular basis of several of these disorders, it is becoming clear that phenotypic pleiotropy exists, that is, the same variant may give rise to a variety of phenotypes, and the classical understanding of these disorders requires a new paradigm. Based on molecular pathogenesis, paroxysmal disorders are now categorized as synaptopathies, transportopathies, channelopathies, second-messenger related disorders, mitochondrial or others. A genetic paradigm also has an advantage of identifying potentially treatable disorders, such as glucose transporter 1 deficiency syndromes, which necessitates a ketogenic diet, and ADCY5 -related disorders, which may respond to caffeine. Clues for a primary etiology include age at onset below 18 years, presence of family history and fixed triggers and attack duration. Paroxysmal movement disorder is a network disorder, with both the basal ganglia and the cerebellum implicated in pathogenesis. Abnormalities in the striatal cAMP turnover pathway may also be contributory. Although next-generation sequencing has restructured the approach to paroxysmal movement disorders, the genetic underpinnings of several entities remain undiscovered. As more genes and variants continue to be reported, these will lead to enhanced understanding of pathophysiological mechanisms and precise treatment.

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“…The primers were designed by PrimerZ 1 . The candidate variants were amplified by PCR using an EasyTaq PCR SuperMix (TransGen Biotech, China) (20). PCR products were then sequenced by Sanger sequencing.…”

Section: Sanger Sequencingmentioning

confidence: 99%

Brain Proteomic Profiling in Intractable Epilepsy Caused by TSC1 Truncating Mutations: A Small Sample Study

Liu

et al. 2020

Front. Neurol.

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Tuberous sclerosis complex (TSC) is a genetic disease characterized by seizures, mental deficiency, and abnormalities of the skin, brain, kidney, heart, and lungs. TSC is inherited in an autosomal dominant manner and is caused by variations in either the TSC1 or TSC2 gene. TSC-related epilepsy (TRE) is the most prevalent and challenging clinical feature of TSC, and more than half of the patients have refractory epilepsy. In clinical practice, we found several patients of intractable epilepsy caused by TSC1 truncating mutations. To study the changes of protein expression in the brain, three cases of diseased brain tissue with TSC1 truncating mutation resected in intractable epilepsy operations and three cases of control brain tissue resected in craniocerebral trauma operations were collected to perform protein spectrum detection, and then the data-independent acquisition (DIA) workflow was used to analyze differentially expressed proteins. As a result, there were 55 up-and 55 down-regulated proteins found in the damaged brain tissue with TSC1 mutation compared to the control. Further bioinformatics analysis revealed that the differentially expressed proteins were mainly concentrated in the synaptic membrane between the patients with TSC and the control. Additionally, TSC1 truncating mutations may affect the pathway of amino acid metabolism. Our study provides a new idea to explore the brain damage mechanism caused by TSC1 mutations.

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Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease

Cited by 4 publications

References 32 publications

Identification of novel mutations in BCKDHB and DBT genes in Vietnamese patients with maple sirup urine disease

Identification of novel mutations in BCKDHB and DBT genes in Vietnamese patients with maple sirup urine disease

Genetic Links to Episodic Movement Disorders: Current Insights

Brain Proteomic Profiling in Intractable Epilepsy Caused by TSC1 Truncating Mutations: A Small Sample Study

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