scholarly journals Case Report: A Novel CACNA1S Mutation Associated With Hypokalemic Periodic Paralysis in a Chinese Family

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie-Yuan Jin ◽  
Bing-Bing Guo ◽  
Yi Dong ◽  
Yue Sheng ◽  
Liang-Liang Fan ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Frameshift Mutation ◽  
Periodic Paralysis ◽  
Chinese Family ◽  
Hypokalemic Periodic Paralysis ◽  
Autosomal Dominant Disorder ◽  
Contraction Coupling ◽  
Voltage Dependent Calcium Channel ◽  
Voltage Dependent ◽  
New Perspective

Hypokalemic periodic paralysis (HypoPP) is a rare autosomal dominant disorder characterized by episodic flaccid paralysis with concomitant hypokalemia. More than half of patients were associated with mutations in CACNA1S that encodes the alpha-1-subunit of the skeletal muscle L-type voltage-dependent calcium channel. Mutations in CACNA1S may alter the structure of CACNA1S and affect the functions of calcium channels, which damages Ca2+-mediated excitation-contraction coupling. In this research, we identified and described a Chinese HypoPP patient with a novel frameshift mutation in CACNA1S [NM_000069.2: c.1364delA (p.Asn455fs)] by targeted sequencing. This study would expand the spectrum of CACNA1S mutations, further our understanding of HypoPP, and provided a new perspective for selecting effective treatments.

scholarly journals Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family

2005 ◽  
Vol 83 (3) ◽  
pp. 203-208 ◽  
Author(s):  
Qiufen Wang ◽  
Mugen Liu ◽  
Chunsheng Xu ◽  
Zhaohui Tang ◽  
Yuhua Liao ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Periodic Paralysis ◽  
Chinese Family ◽  
Hypokalemic Periodic Paralysis

scholarly journals Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a South American family

2009 ◽  
Vol 54 (11) ◽  
pp. 660-664 ◽  
Author(s):  
Tie Ke ◽  
Cladelis Rubio Gomez ◽  
Heidi Eliana Mateus ◽  
Juan Andres Castano ◽  
Qing Kenneth Wang
Keyword(s):  
Autosomal Dominant ◽  
Periodic Paralysis ◽  
South American ◽  
American Family ◽  
Hypokalemic Periodic Paralysis

scholarly journals A Novel Frameshift Mutation of SCNN1G Causing Liddle Syndrome with Normokalemia

2019 ◽  
Vol 32 (8) ◽  
pp. 752-758
Author(s):  
Peng Fan ◽  
Yu-Mo Zhao ◽  
Di Zhang ◽  
Ying Liao ◽  
Kun-Qi Yang ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Frameshift Mutation ◽  
Stop Codon ◽  
Single Gene ◽  
Family Members ◽  
Premature Stop Codon ◽  
Chinese Family ◽  
Autosomal Dominant Disorder ◽  
Liddle Syndrome ◽  
Genetic Sequencing

Abstract BACKGROUND Liddle syndrome (LS) is an autosomal dominant disorder caused by single-gene mutations of the epithelial sodium channel (ENaC). It is characterized by early-onset hypertension, spontaneous hypokalemia and low plasma renin and aldosterone concentrations. In this study, we reported an LS pedigree with normokalemia resulting from a novel SCNN1G frameshift mutation. METHODS Peripheral blood samples were collected from the proband and eight family members for DNA extraction. Next-generation sequencing and Sanger sequencing were performed to identify the SCNN1G mutation. Clinical examinations were used to comprehensively evaluate the phenotypes of two patients. RESULTS Genetic analysis identified a novel SCNN1G frameshift mutation, p.Arg586Valfs*598, in the proband with LS. This heterozygous frameshift mutation generated a premature stop codon and deleted the vital PY motif of ENaC. The same mutation was present in his elder brother with LS, and his mother without any LS symptoms. Biochemical examination showed normokalemia in the three mutation carriers. The mutation identified was not found in any other family members, 100 hypertensives, or 100 healthy controls. CONCLUSIONS Our study identified a novel SCNN1G frameshift mutation in a Chinese family with LS, expanding the genetic spectrum of SCNN1G. Genetic testing helped us identify LS with a pathogenic mutation when the genotypes and phenotype were not completely consistent because of the hypokalemia. This case emphasizes that once a proband is diagnosed with LS by genetic testing, family genetic sequencing is necessary for early diagnosis and intervention for other family members, to protect against severe cardiovascular complications.

scholarly journals A Novel Mutation ofSMAD3Identified in a Chinese Family with Aneurysms-Osteoarthritis Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Wenwen Zhang ◽  
Min Zhou ◽  
Cheng Liu ◽  
Chen Liu ◽  
Tong Qiao ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Early Onset ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Mutation Spectrum ◽  
Chinese Family ◽  
Phenotype Correlation ◽  
Autosomal Dominant Disorder ◽  
Arterial Tree ◽  
Craniofacial Features

Aneurysms-osteoarthritis syndrome (AOS) is a recently delineated autosomal dominant disorder characterized by aneurysms, dissections, and tortuosity throughout the arterial tree in association with early onset osteoarthritis, mild craniofacial features, and skeletal and cutaneous anomalies. Previous studies have demonstrated that mutations inSMAD3, a key regulator of TGF-βsignal transduction, contribute to AOS. Here, we investigated a family of three generations affected by AOS. A novelSMAD3mutation, c.266G>A (p.C89Y), was identified and cosegregated with the affected individuals in this family. Our finding expands the mutation spectrum ofSMAD3gene and further strengthens the connection between the presence of aneurysms-osteoarthritis phenotype andSMAD3mutations, which facilitates the understanding of the genotype-phenotype correlation of AOS.

scholarly journals Hypokalemic periodic paralysis: a case report

2019 ◽  
Vol 1 (Number 2) ◽  
pp. 29-31
Author(s):  
Golam Nabi ◽  
Fahmida Ferdou ◽  
Sadika Kadir ◽  
Sarah Ambarin Chowdhury ◽  
Mohammad Babul Miah ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Sudden Onset ◽  
Periodic Paralysis ◽  
Laboratory Evaluation ◽  
Hypokalemic Periodic Paralysis ◽  
Skeletal Muscle Weakness ◽  
Low Potassium ◽  
Carbohydrate Load ◽  
Rare Group

Hypokalemic periodic paralysis (HKPP) is a rare genetic disorder with autosomal dominant inheritance and characterized by recurrent attacks of skeletal muscle weakness with associated hypokalemia which is precipitated by stress, cold, carbohydrate load, infection, glucose infusion, hypothermia, metabolic alkalosis, anesthesia and steroids. Hypokalemic Periodic Paralysis is one form of Periodic Paralysis, a rare group of disorders that can cause of sudden onset weakness. A case of a 29 year old male is presented here. The patient presented with sudden onset paralysis of his extremities. Laboratory evaluation revealed a markedly low potassium level. The patient’s paralysis resolved upon repletion of his low potassium and he was discharged with no neurologic deficits. Although rare, Periodic Paralysis must differentiated from other causes of weakness and paralysis so that the proper treatment can be initiated quickly.

scholarly journals Morphological Alterations of the Sarcotubular System in Permanent Myopathy of Hereditary Hypokalemic Periodic Paralysis with a Mutation in the CACNA1S Gene

2020 ◽  
Vol 79 (12) ◽  
pp. 1276-1292
Author(s):  
Takamura Nagasaka ◽  
Takanori Hata ◽  
Kazumasa Shindo ◽  
Yoshiki Adachi ◽  
Megumi Takeuchi ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Repair Process ◽  
Periodic Paralysis ◽  
Immunohistochemical Localization ◽  
Morphological Observation ◽  
Hypokalemic Periodic Paralysis ◽  
Morphological Alterations ◽  
Contraction Coupling ◽  
Sarcotubular System ◽  
T Tubules

Abstract We investigated the immunohistochemical localization of several proteins related to excitation-contraction coupling and ultrastructural alterations of the sarcotubular system in biopsied muscles from a father and a daughter in a family with permanent myopathy with hypokalemic periodic paralysis (PMPP) due to a mutation in calcium channel CACNA1S; p. R1239H hetero. Immunostaining for L-type calcium channels (LCaC) showed linear hyper-stained regions indicating proliferation of longitudinal t-tubules. The margin of vacuoles was positive for ryanodine receptor, LCaC, calsequestrin (CASQ) 1, CASQ 2, SR/ER Ca2+-ATPase (SERCA) 1, SERCA2, dysferlin, dystrophin, α-actinin, LC3, and LAMP 1. Electron microscopy indicated that the vacuoles mainly originated from the sarcoplasmic reticulum (SR). These findings indicate impairment of the muscle contraction system related to Ca2+ dynamics, remodeling of t-tubules and muscle fiber repair. We speculate that PMPP in patients with a CACNA1S mutation might start with abnormal SR function due to impaired LCaC. Subsequent induction of muscular contractile abnormalities and the vacuoles formed by fused SR in the repair process including autophagy might result in permanent myopathy. Our findings may facilitate prediction of the pathomechanisms of PMPP seen on morphological observation.

scholarly journals A family with Milroy disease caused by the FLT4/VEGFR3 gene variant c.2774 T > A

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yu Sui ◽  
Yongping Lu ◽  
Meina Lin ◽  
Xiang Ni ◽  
Xinren Chen ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
In Silico ◽  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Large Family ◽  
Missense Variant ◽  
Chinese Family ◽  
Healthy Controls ◽  
Gene Variant ◽  
Autosomal Dominant Disorder

Abstract Background Milroy disease (MD) is a rare, autosomal-dominant disorder. Variants in the Fms-related tyrosine kinase 4 (FLT4/VEGFR3) gene cause the symptoms of this disease. In this report, we investigated the variant in a large Chinese family with MD. Methods We conducted Sanger sequencing of exons 17–26 of FLT4/VEGFR3 (NM_182925.4). We assessed its pathogenicity based on the ACMG criteria and predicted it with an in silico program. Results A heterozygous substitution (NM_182925.4 (FLT4/VEGFR3):c.2774 T>A, p. (Val925Glu)) was detected in all patients with MD but not in any healthy controls. The variant was evaluated as pathogenic according to the ACMG criteria and was predicted to be pathogenic using an in silico program. Conclusions In this report, we described a large family with MD caused by a missense variant in FLT4/VEGFR3 (NM_182925.4 (FLT4/VEGFR3_v001):c.2774 T>A, p. (Val925Glu)). There are phenotypic heterogeneities among family members, and further research should be conducted to explore the possible reasons.

scholarly journals A Novel Splicing Mutation ofKITResults in Piebaldism and Auburn Hair Color in a Chinese Family

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yong-jia Yang ◽  
Rui Zhao ◽  
Xin-yu He ◽  
Li-ping Li ◽  
Ke-wei Wang ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Mutation Screening ◽  
Chinese Family ◽  
Hair Color ◽  
Splicing Mutation ◽  
Autosomal Dominant Disorder ◽  
Kit Mutation ◽  
Key Characteristics ◽  
Color Variant

Piebaldism is a rare autosomal dominant disorder of melanocyte development, which is mostly caused byKITgene. The key characteristics of piebaldism include localized poliosis, congenital leukoderma, and other variable manifestations. The previous study has illustrated that the homogeneousMC1R(a gene which is associated with the hair color) variant (p.I120T) coordinating withKITmutation may lead to auburn hair color and piebaldism. In this study, we have investigated a Chinese family with piebaldism and auburn hair color; the mutation screening ofKITandMC1Rgenes identified that only a splicing mutation (c. 2484+1G>A) ofKITgene cosegregated with the auburn hair color and piebaldism. The data of this study and others suggests that the KIT mutation may causes of the auburn hair color in the piebaldism patients.

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