A Novel mutation in the SLC26A4 gene in a Chinese family with Pendred syndrome

Abstract Context: We studied two families from Galicia (northwest Spain) with Pendred syndrome (PS) and unusual thyroid phenotypes. In family A, the proposita had a large goiter and hypothyroxinemia but normal TSH and free T3 (FT3). In family B, some affected members showed deafness but not goiter. Objective: Our objective was to identify the mutations causing PS and molecular mechanisms underlying the thyroid phenotypes. Interventions: Interventions included extraction of DNA and of thyroid tissue. Patients: Propositi and 10 members of the two families participated in the study. Main Outcome Measures: Main outcome measures included SLC26A4 gene analysis, deiodinase activities in thyroid tissue, and c.416–1G→A effects on SLC26A4 splicing. In addition, a primary PS thyrocyte culture, T-PS2, was obtained from propositus B and compared with another culture of normal human thyrocytes, NT, by Western blotting, confocal microscopy, and iodine uptake kinetics. Results: Proposita A was heterozygous for c.578C→T and c.279delT, presented with goiter, and had normal TSH and FT3 but low FT4 attributable to high type 1 and type 2 iodothyronine deiodinase activities in the goiter. Propositus B bore c.279delT and a novel mutation c.416–1G→A; some deaf relatives were homozygous for c.416–1G→A but did not present goiter. The c.279delT mutation was associated with identical haplotype in the two families. T-PS2 showed truncated pendrin retained intracellularly and high iodine uptake with low efflux leading to iodine retention. Conclusions: c.279delT is a founder mutation in Galicia. Proposita A adapted to poor organification by increasing deiodinase activities in the goiter, avoiding hypothyroidism. Lack of goiter in subjects homozygous for c.416–1G→A was due to incomplete penetrance allowing synthesis of some wild-type pendrin. Intracellular iodine retention, as seen in T-PS2, could play a role in thyroid alterations in PS.

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A Novel Mutation of Notch homolog protein 2 gene in a Chinese Family with Hajdu-Cheney Syndrome

Chinese Medical Journal ◽

10.4103/0366-6999.219141 ◽

2017 ◽

Vol 130 (23) ◽

pp. 2883-2884 ◽

Cited By ~ 2

Author(s):

Ruo-Lan Gong ◽

Jing Wu ◽

Tong-Xin Chen

Keyword(s):

Novel Mutation ◽

Chinese Family

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Novel compound heterozygous EYS variants may be associated with arRP in a large Chinese pedigree

Bioscience Reports ◽

10.1042/bsr20193443 ◽

2020 ◽

Vol 40 (6) ◽

Cited By ~ 1

Author(s):

Chunli Wei ◽

Ting Xiao ◽

Jingliang Cheng ◽

Jiewen Fu ◽

Qi Zhou ◽

...

Keyword(s):

Novel Mutation ◽

Gene Mutations ◽

Chinese Family ◽

Compound Heterozygous ◽

Missense Mutations ◽

The Novel ◽

Pathogenic Variants ◽

Pathogenic Genes ◽

Compound Heterozygous Variants ◽

Normal Controls

Abstract As a genetically heterogeneous ocular dystrophy, gene mutations with autosomal recessive retinitis pigmentosa (arRP) in patients have not been well described. We aimed to detect the disease-causing genes and variants in a Chinese arRP family. In the present study, a large Chinese pedigree consisting of 31 members including a proband and another two patients was recruited; clinical examinations were conducted; next-generation sequencing using a gene panel was used for identifying pathogenic genes, and Sanger sequencing was performed for verification of mutations. Novel compound heterozygous variants c.G2504A (p.C835Y) and c.G6557A (p.G2186E) for the EYS gene were identified, which co-segregated with the clinical RP phenotypes. Sequencing of 100 ethnically matched normal controls didn’t found these mutations in EYS. Therefore, our study identified pathogenic variants in EYS that may cause arRP in this Chinese family. This is the first study to reveal the novel mutation in the EYS gene (c.G2504A, p.C835Y), extending its mutation spectrum. Thus, the EYS c.G2504A (p.C835Y) and c.G6557A (p.G2186E) variants may be the disease-causing missense mutations for RP in this large arRP family. These findings should be helpful for molecular diagnosis, genetic counseling and clinical management of arRP disease.

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A Novel COMP Mutated Allele Identified in a Chinese Family with Pseudoachondroplasia

BioMed Research International ◽

10.1155/2021/6678531 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Bing-Bing Guo ◽

Jie-Yuan Jin ◽

Zhuang-Zhuang Yuan ◽

Lei Zeng ◽

Rong Xiang

Keyword(s):

Extracellular Matrix ◽

Cartilage Oligomeric Matrix Protein ◽

Matrix Protein ◽

Autosomal Dominant ◽

Novel Mutation ◽

Chinese Family ◽

The Novel ◽

Structure Model ◽

Whole Exome ◽

Nucleotide Mutation

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia with an estimated incidence of ~1/60000 that is characterized by disproportionate short stature, brachydactyly, joint laxity, and early-onset osteoarthritis. COMP encodes the cartilage oligomeric matrix protein, which is expressed predominantly in the extracellular matrix (ECM) surrounding the cells that make up cartilage, ligaments, and tendons. Mutations in COMP are known to give rise to PSACH. In this study, we identified a novel nucleotide mutation (NM_000095.2: c.1317C>G, p.D439E) in COMP responsible for PSACH in a Chinese family by employing whole-exome sequencing (WES) and built the structure model of the mutant protein to clarify its pathogenicity. The novel mutation cosegregated with the affected individuals. Our study expands the spectrum of COMP mutations and further provides additional genetic testing information for other PSACH patients.

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A novel mutation in the conserved sequence of vascular endothelial growth factor receptor 3 leads to primary lymphoedema

Journal of International Medical Research ◽

10.1177/0300060518773264 ◽

2018 ◽

Vol 46 (8) ◽

pp. 3162-3171 ◽

Cited By ~ 3

Author(s):

Ting Dai ◽

Bohan Li ◽

Bo He ◽

Liwei Yan ◽

Liqiang Gu ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Novel Mutation ◽

Family Members ◽

Growth Factor Receptor ◽

Chinese Family ◽

Vascular Endothelial ◽

Healthy Controls ◽

Endothelial Growth Factor ◽

Congenital Lymphoedema

Objective To investigate whether lymphoedema in a Chinese family showed the hereditary and clinical characteristics of Milroy disease, an autosomal dominant form of congenital lymphoedema, typically characterized by chronic lower limb tissue swelling due to abnormal lymphatic vasculature development, and to perform mutational analyses of vascular endothelial growth factor receptor ( VEGFR)3. Methods Individuals from a three-generation family affected by congenital lymphoedema were clinically assessed for Milroy disease. Mutation analysis of VEGFR3 was performed using DNA from family members and healthy controls. Results Out of 20 family members, eight were diagnosed with hereditary lymphoedema. Mutation analyses revealed a novel mutation site for c.3163 G>A, resulting in a p.1055D>N mutation in the second tyrosine kinase domain of VEGFR3, which was present in affected individuals only (absent in all unaffected family members and 130 healthy controls). Computed functional analyses showed the mutation may lead to structural alterations with a probability of 0.99999 of being disease causing. Conclusion A novel mutation associated with Milroy disease was identified in a Chinese family, expanding our knowledge of VEGFR3 gene function and providing a potential molecular target for treating hereditary lymphoedema.

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PHKG2 mutation spectrum in glycogen storage disease type IXc: a case report and review of the literature

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0170 ◽

2018 ◽

Vol 31 (3) ◽

pp. 331-338 ◽

Cited By ~ 4

Author(s):

Chunyun Li ◽

Lihua Huang ◽

Lang Tian ◽

Jia Chen ◽

Shentang Li ◽

...

Keyword(s):

Gene Mutation ◽

Glycogen Storage Disease ◽

Storage Disease ◽

Novel Mutation ◽

Glycogen Storage Disease Type ◽

Glycogen Storage ◽

Disease Type ◽

Mutation Spectrum ◽

Chinese Family ◽

Phosphorylase Kinase

AbstractBackground:PHKG2gene mutation can lead to liver phosphorylase kinase (PhK) deficiency, which is related to glycogen storage disease type IX (GSD IX). GSD IXc due toPHKG2mutation is the second most common GSD IX.Methods:We identified a novel mutation (c.553C>T, p.Arg185X) inPHKG2in a Chinese family and verified it by next-generation and Sanger sequencing. The mutation spectrum of thePHKG2gene was summarized based on 25 GSD IXc patients withPHKG2mutations.Results:We found that missense mutation (39%) was the most common type of mutation, followed by nonsense mutation (23%). Mutations were more prevalent in Asian (12/25) and European (9/25) populations than in populations from elsewhere. The exons had more sites of mutation than the introns, and exons 3 and 6 were the most frequent sites of mutations.Conclusions:This study expands our knowledge of thePHKG2gene mutation spectrum, providing a molecular basis for GSD IXc.

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