A novel mutation of keratin 9 in a large Chinese family with epidermolytic palmoplantar keratoderma

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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Spectrum of Ankyrin Mutations in Hereditary Spherocytosis: A Case Report and Review of the Literature

Acta Haematologica ◽

10.1159/000492024 ◽

2018 ◽

Vol 140 (2) ◽

pp. 77-86 ◽

Cited By ~ 1

Author(s):

Yeping Luo ◽

Zhuoying Li ◽

Lihua Huang ◽

Jing Tian ◽

Menglong Xiong ◽

...

Keyword(s):

Hereditary Spherocytosis ◽

Novel Mutation ◽

Laboratory Data ◽

Clinical Manifestations ◽

Mutation Spectrum ◽

Chinese Family ◽

Review Of The Literature ◽

Newborn Period ◽

Gene Splicing ◽

Generation Sequencing

Background/Aims: Hereditary spherocytosis (HS) is a common pediatric hemolytic anemia caused by congenital red blood cell defects. HS due to ankyrin 1 (ANK1) mutations is the most common type. We explored an ANK1 mutation from an HS patient and reviewed the literature. Methods: We detected the mutation in a Chinese family in which 2 members were diagnosed with HS by next-generation sequencing. The proband was diagnosed with HS in the newborn period, based on clinical manifestations, laboratory data, and family history. The mutation spectrum of the ANK1 gene was summarized based on 85 patients diagnosed with HS carrying ANK1 mutations, and the ANK1 mutation spectrum was summarized and analyzed. Results: We identified a novel mutation affecting ANK1 gene splicing (a splicing mutation) in both the patient and her mother, which is a substitution of T>G 2 nt after exon 25 in intron 26. The study expands our knowledge of the ANK1 gene mutation spectrum, providing a molecular basis for HS. Conclusion: A novel ANK1 mutation (NM_000037.3, c.2960+2T>G, intron 26) that is potentially associated with HS was identified. To date, 80 ANK1 mutations have been reported to be associated with HS in humans.

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A novel variant in PAX6 as the cause of aniridia in a Chinese family

10.21203/rs.3.rs-21412/v2 ◽

2020 ◽

Author(s):

Xin Jin ◽

Wei Liu ◽

HouBin Huang

Keyword(s):

Nonsense Mutation ◽

Novel Mutation ◽

Causative Mutation ◽

Chinese Family ◽

The Novel ◽

Targeted Next Generation Sequencing ◽

Iris Defect ◽

The Family ◽

Novel Variant ◽

Pax6 Mutation

Abstract Background: Aniridia is a kind of congenital human panocular anomaly, which is related to PAX6 commonly. Methods: A Chinese Aniridia pedigree underwent ophthalmic examinations, including visual acuity, slit lamp and fundoscopy examination. The targeted next-generation sequencing of Aniridia genes was used to identify the causative mutation. Results: A novel heterozygous PAX6 nonsense mutation c.619A>T (p.K207*) was identified in the Chinese autosomal dominant family with aniridia. Phenotypes related to the novel mutation include nystagmus, iris defect, cataract and absence of macular fovea. Conclusion: The novel nonsense mutation in PAX6 was responsible for aniridia phenotype in the family. which expands the spectrum of the PAX6 mutation and its associated phenotype.

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