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.

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 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 Mild Encephalitis/Encephalopathy with Reversible Splenial Lesion (MERS) due to Acute Intermittent Porphyria with a novel mutation in the porphobinoglien deaminase gene

2020 ◽  
Author(s):  
xiaoqing li ◽  
fei han ◽  
qianlong chen ◽  
tienan zhu ◽  
yongqiang zhao ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Stop Codon ◽  
Novel Mutation ◽  
Acute Intermittent Porphyria ◽  
Porphobilinogen Deaminase ◽  
Splicing Mutation ◽  
Autosomal Dominant Disorder ◽  
The Third ◽  
Splenial Lesion ◽  
Partial Deficiency

Abstract Background: Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by a reversible isolated lesion with transiently reduced diffusion in the central portion of the splenium of the corpus callosum (SCC). The reason for MERS is unknown. however, infectious-related MERS (in particular virus) remains the most common cause of reversible splenial lesions. Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a partial deficiency of porphobilinogen deaminase (PBGD), the third enzyme in the of hemebiosynthetic pathway. It can affect the autonomic, peripheral, and central nervous system. Result: In this study, we report a 20-year-old woman with AIP who presented with MR manifestations suggestive of MERS, she had a novel PBGD splicing mutation, a G to A mutation in base 594 resulting in tryptophan to a stop codon (W198*). Conclusion: To the best of our knowledge, this is only one published case of MERS associated with AIP.

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 Hypertension and Brachydactyly Syndrome Associated With Vertebral Artery Malformation Caused by a PDE3A Missense Mutation

2019 ◽  
Author(s):  
Peng Fan ◽  
Di Zhang ◽  
Kun-Qi Yang ◽  
Qiong-Yu Zhang ◽  
Fang Luo ◽  
...  
Keyword(s):  
Vertebral Artery ◽  
Missense Mutation ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Autosomal Dominant Disorder ◽  
Conserved Domain ◽  
Long Term Follow Up ◽  
Generation Sequencing

Abstract BACKGROUND Hypertension and brachydactyly syndrome (HTNB), also called Bilginturan syndrome, is a rare autosomal dominant disorder characterized by severe salt-independent hypertension, a short stature, brachydactyly, and death from stroke before the age of 50 years when untreated. The purpose of the present study was to identify a PDE3A mutation leading to HTNB associated with vertebral artery malformation in a Chinese family. METHODS Peripheral blood samples were collected from all subjects for DNA extraction. Next-generation sequencing and Sanger sequencing were performed to identify the PDE3A mutation. A comparative overview was performed in the probands with HTNB caused by PDE3A mutations. RESULTS Genetic analysis identified a missense mutation in PDE3A, c.1346G>A, in the proband with HTNB. This mutation, resulting in p.Gly449Asp, was located in a highly conserved domain and predicted to be damaging by different bioinformatics tools. Cosegregation analyses showed that the proband inherited the identified mutation from her father. Antihypertensive therapy was effective for the proband. Comparative overview of HTNB probands with 9 different PDE3A mutations revealed phenotypic heterogeneity. CONCLUSIONS Genetic screening can significantly improve the diagnosis of HTNB patients at an early age. Our study not only adds to the spectrum of PDE3A mutations in the Chinese population and extends the phenotype of HTNB patients to include vertebral malformation but also improves the awareness of pathogenesis in HTNB patients. We emphasize the importance of antihypertensive treatment and long-term follow-up to prevent stroke and adverse cardiovascular events.

scholarly journals A novel variant of IHH in a Chinese family with brachydactyly type 1

2019 ◽  
Author(s):  
Qi Yang ◽  
Jin Wang ◽  
Xiaoxian Tian ◽  
Fei Chen ◽  
Jing Lan ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Missense Variant ◽  
Chinese Family ◽  
Indian Hedgehog ◽  
Autosomal Dominant Disorder ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Novel Variant ◽  
Active Fragment

Abstract Brachydactyly type A1(BDA-1) is an autosomal dominant disorder which is caused by heterozygous pathogenic variants in a specific region of the N-terminal active fragment of Indian Hedgehog ( IHH ). The disorder is mainly characterized by shortening or missing of the middle phalanges. The following study revealed a novel heterozygous missense variant c.299A>G (p.D100G) at the mutational hotspot of IHH gene after performing whole-exome sequencing in the proband of a Chinese family with BDA-1. The variant co-segregated with BDA-1 in the pedigree, showed 100% penetrance for phalange phenotype with variable expressivity. This finding expanded the variants on IHH gene which contribute to the cause of BDA-1.

scholarly journals A Milroy Disease Family Caused by FLT4 Gene Mutation of c.2774 T>A

2021 ◽  
Author(s):  
Yu Sui ◽  
Yongping lu ◽  
Meina Lin ◽  
Xiang Ni ◽  
Xinren Chen ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Large Family ◽  
Chinese Family ◽  
Autosomal Dominant Disorder ◽  
Amplification System ◽  
Reverse Primer ◽  
Dna Template ◽  
Disease Family ◽  
Forward Primer

Abstract Background: Milroy disease (MD) is a rare, autosomal dominant disorder. Mutations in the Fms-related tyrosine kinase 4 (FLT4) gene cause the symptoms of this disease. In this report, we investigated the mutations in a large Chinese family with MD.Methods: We conducted Sanger sequencing of exons 17–26 of the FLT4 (NM_182925.4) gene. The primers were as follows: forward, 5' CTTCATCAGCGTCGAGTGG 3' and reverse, 5' ATTATGGGCGGGTTCCTT 3'. The amplification system is as follows: 2×Biotech Power PCR Mix, 10 µl; forward primer, 0.8 µl (10 µM); reverse primer, 0.8 µl (10 µM); DNA template, 1 µl (50 ng/µl); and ddH2O, 13.4 µl. The mutation was evaluated with MutationTaster, SIFT and PolyPhen.Results: A heterozygous substitution was detected in all patients but not in any healthy controls (FLT4 gene: c.2774 T>A, p.V925E). The mutation was predicted to be pathogenic.Conclusions: In this report, we described a large family with MD caused by a missense mutation of the FLT4 gene (c.2774 T>A, p.V925E).

scholarly journals A novel variant of IHH in a Chinese family with brachydactyly type 1

2020 ◽  
Author(s):  
Qi Yang ◽  
Jin Wang ◽  
Xiaoxian Tian ◽  
Fei Chen ◽  
Jing Lan ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Missense Variant ◽  
Chinese Family ◽  
Indian Hedgehog ◽  
Autosomal Dominant Disorder ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Novel Variant ◽  
Active Fragment

Abstract Brachydactyly type A1(BDA-1) is an autosomal dominant disorder which is caused by heterozygous pathogenic variants in a specific region of the N-terminal active fragment of Indian Hedgehog ( IHH ). The disorder is mainly characterized by shortening or missing of the middle phalanges. The following study revealed a novel heterozygous missense variant c.299A>G (p.D100G) at the mutational hotspot of IHH gene after performing whole-exome sequencing in the proband of a Chinese family with BDA-1. The variant co-segregated with BDA-1 in the pedigree, showed 100% penetrance for phalange phenotype with variable expressivity. This finding expanded the variants on IHH gene which contribute to the cause of BDA-1.

scholarly journals A novel pathogenic variant of IHH for Brachydactyly type A1

2019 ◽  
Author(s):  
Qi Yang ◽  
Jin Wang ◽  
Xiaoxian Tian ◽  
Fei Chen ◽  
Jing Lan ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Autosomal Dominant ◽  
Missense Variant ◽  
Specific Region ◽  
Chinese Family ◽  
Indian Hedgehog ◽  
Autosomal Dominant Disorder ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Active Fragment

Abstract Brachydactyly type A1 (BDA-1, MIM 112500) is a genetically heterogeneous autosomal-dominant disorder mainly characterized by shortening or missing of the middle phalanges. Brachydactyly type A1 (BDA-1) is caused by heterozygous pathogenic variants in a specific region of the N-terminal active fragment of Indian Hedgehog (IHH). In this study, we reported a Chinese family with 8 members affected with Brachydactyly type A1. After performing whole-exome sequencing in the proband, we identified a novel heterozygous missense variant c.299A>G (p.D100G) at the mutational hotspot of IHH gene. The variant co-segregated with BDA-1 in the pedigree, showed 100% penetrance for phalange phenotype with variable expressivity. This finding expanded the Brachydactyly type A1-related mutational spectrum of IHH gene.

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