scholarly journals Two novel mutations in PRPF3 causing autosomal dominant retinitis pigmentosa

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Zilin Zhong ◽  
Min Yan ◽  
Wan Sun ◽  
Zehua Wu ◽  
Liyun Han ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Chinese Population ◽  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Photoreceptor Cells ◽  
Eye Diseases ◽  
Novel Mutations ◽  
Whole Exome ◽  
Selective Death ◽  
Exon 11

Abstract Retinitis pigmentosa (RP) is a heterogeneous set of hereditary eye diseases, characterized by selective death of photoreceptor cells in the retina, resulting in progressive visual impairment. Approximately 20–40% of RP cases are autosomal dominant RP (ADRP). In this study, a Chinese ADRP family previously localized to the region between D1S2819 and D1S2635 was sequenced via whole-exome sequencing and a variant c.1345C > G (p.R449G) was identified in PRPF3. The Sanger sequencing was performed in probands of additional 95 Chinese ADRP families to investigate the contribution of PRPF3 to ADRP in Chinese population and another variant c.1532A > C (p.H511P) was detected in one family. These two variants, co-segregate with RP in two families respectively and both variants are predicted to be pathological. This is the first report about the spectrum of PRPF3 mutations in Chinese population, leading to the identification of two novel PRPF3 mutations. Only three clustered mutations in PRPF3 have been identified so far in several populations and all are in exon 11. Our study expands the spectrum of PRPF3 mutations in RP. We also demonstrate that PRPF3 mutations are responsible for 2.08% of ADRP families in this cohort indicating that PRPF3 mutations might be relatively rare in Chinese ADRP patients.

scholarly journals RHOMutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Satoshi Katagiri ◽  
Takaaki Hayashi ◽  
Masakazu Akahori ◽  
Takeshi Itabashi ◽  
Jo Nishino ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Conformational Transition ◽  
Novel Mutation ◽  
The Novel ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Modeling Analysis ◽  
Whole Exome ◽  
The Impact

Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO) mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP).Methods. Whole-exome sequence analysis was performed in ten adRP families. IdentifiedRHOmutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of theRHOmutation on the rhodopsin conformation was examined by molecular modeling analysis.Results. In two adRP families, we identified twoRHOmutations (c.377G>T (p.W126L) and c.1036G>C (p.A346P)), one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L) might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP.Conclusions. Our findings demonstrated that the novel mutation (p.W126L) may be associated with the phenotype of sector RP. Identification ofRHOmutations is a very useful tool for predicting disease severity and providing precise genetic counseling.

Digenic Inheritance in Juvenile Open-Angle Glaucoma

2021 ◽  
Author(s):  
Bindu I. Somarajan ◽  
Shikha Gupta ◽  
Karthikeyan Mahalingam ◽  
Kishan Azmira ◽  
Viney Gupta
Keyword(s):  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Open Angle Glaucoma ◽  
Open Angle ◽  
Northern India ◽  
Digenic Inheritance ◽  
Whole Exome ◽  
The Family ◽  
Primary Glaucoma ◽  
Study Participants

AbstractJuvenile open-angle glaucoma (JOAG) is an uncommon subset of primary glaucoma with an onset before the age of 40 years. In this case report, we describe the cosegregation of MYOC, p.Pro370Leu and LTBP2, p.Pro432Leu mutations in a family with JOAG. The family with autosomal dominant JOAG belonged to Northern India. The samples of proband and her parents were evaluated by whole exome sequencing. Sanger sequencing was conducted in all the study participants to check the mutations identified. Both MYOC and LTBP2 mutations were found to cosegregate in affected individuals leading to a severe JOAG phenotype, thereby suggesting a digenic inheritance of MYOC with LTBP2 in this family.

Prevalence and associated phenotypes of DUSP6, IL17RD and SPRY4 variants in a large Chinese cohort with isolated hypogonadotropic hypogonadism

2020 ◽  
Vol 58 (1) ◽  
pp. 66-72
Author(s):  
Meichao Men ◽  
Xinying Wang ◽  
Jiayu Wu ◽  
Wang Zeng ◽  
Fang Jiang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Sanger Sequencing ◽  
Segregation Analysis ◽  
Autosomal Dominant ◽  
Hypogonadotropic Hypogonadism ◽  
Chinese Patients ◽  
Biological Processes ◽  
Blue Colour ◽  
Whole Exome ◽  
Chinese Cohort

BackgroundFGF8-FGFR1 signalling is involved in multiple biological processes, while impairment of this signalling is one of the main reasons for isolated hypogonadotropic hypogonadism (IHH). Recently, several negative modulators of FGF8-FGFR1 signalling were also found to be involved in IHH, including DUSP6, IL17RD, SPRY2 and SPRY4. The aim of this study was to investigate the genotypic and phenotypic spectra of these genes in a large cohort of Chinese patients with IHH.MethodsA total of 196 patients with IHH were enrolled in this study. Whole-exome sequencing was performed to identify variants, which was verified by PCR and Sanger sequencing.ResultsFour heterozygous DUSP6 variants (p.S157I, p.R83Q, p.P188L and p.N355I) were found in six patients. Cryptorchidism, dental agenesis, syndactyly and blue colour blindness were commonly observed in patients with DUSP6 mutations. Six heterozygous IL17RD variants (p.P191L, p.G35V, p.S671L, p.A221T, p.I329M and p.I329V) were found in seven patients. Segregation analysis indicated that 100% (5/5) of probands inherited the IL17RD variants from their unaffected parents, and oligogenicity was found in 4/7 patients. One rare SPRY4 variant (p.T68S) was found in a female patient with Kallmann syndrome who also carried a PLXNA1 mutation.ConclusionOur study greatly enriched the genotypic and phenotypic spectra of DUSP6, IL17RD and SPRY4 in IHH. Mutations in DUSP6 alone seem sufficient to cause IHH in an autosomal dominant manner, whereas IL17RD or SPRY4 mutations may cause IHH phenotypes in synergy with variants in other IHH-associated genes.

Three novel mutations (P215L, T289P, and 3811-2 A?G) in the rhodopsin gene in autosomal dominant retinitis pigmentosa in Spanish families

2000 ◽  
Vol 16 (1) ◽  
pp. 95-96 ◽  
Author(s):  
Mar�a Martinez-Gimeno ◽  
Mar�a Jos� Trujillo ◽  
Isabel Lorda ◽  
Ascensi�n Gimenez ◽  
Mar�a Teresa Calvo ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Novel Mutations ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Rhodopsin Gene

scholarly journals Identification of Two Novel Frameshift Mutations in Exostosin 1 in Two Families with Multiple Osteochondromas

2021 ◽  
pp. 1-5
Author(s):  
Chen-Yu Wang ◽  
Fang Yu ◽  
Jie-Yuan Jin ◽  
Ji-Qiang He ◽  
Liang-Liang Fan ◽  
...  
Keyword(s):  
Skeletal Dysplasia ◽  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Genetic Diagnosis ◽  
Long Bones ◽  
Novel Mutations ◽  
Frameshift Mutations ◽  
Glycosyl Transferase ◽  
Multiple Osteochondromas ◽  
Conserved Domain

Multiple osteochondromas (MO) is an autosomal dominant hereditary disorder, which typically manifests as skeletal dysplasia, mainly involving long bones and knees, ankles, elbows, wrists, shoulders, and pelvis. Previous studies have demonstrated that mutations in exostosin glycosyl transferase-1 (<i>EXT1</i>) and exostosin glycosyl transferase-2 (<i>EXT2</i>) were the main cause of MO. In this study, we enrolled 2 families with MO. Sanger sequencing revealed 2 novel frameshift mutations – c.1432_1433insCCCCCCT; p.Lys479Profs*44 and c.1431_1431delC; p.S478PfsX10 – in the <i>EXT1</i> gene detected in 2 families, respectively. Both novel mutations, located in the conserved domain of EXT1 and predicted to be disease causing by informatics programs, were absent in our 200 control cohorts and other public databases. Our study expanded the spectrum of <i>EXT1</i> mutations and contributed to genetic diagnosis and counseling of patients with MO.

Whole Exome Sequencing in Thai Patients With Retinitis Pigmentosa Reveals Novel Mutations in Six Genes

2014 ◽  
Vol 55 (4) ◽  
pp. 2259 ◽  
Author(s):  
Worapoj Jinda ◽  
Todd D. Taylor ◽  
Yutaka Suzuki ◽  
Wanna Thongnoppakhun ◽  
Chanin Limwongse ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutations ◽  
Whole Exome ◽  
Six Genes

scholarly journals Application of Whole Exome Sequencing in Six Families with an Initial Diagnosis of Autosomal Dominant Retinitis Pigmentosa: Lessons Learned

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0133624 ◽  
Author(s):  
Berta Almoguera ◽  
Jiankang Li ◽  
Patricia Fernandez-San Jose ◽  
Yichuan Liu ◽  
Michael March ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Lessons Learned ◽  
Initial Diagnosis ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Whole Exome

scholarly journals Analysis of the Genetic Characteristics of a Chinese Family With Otosclerosis

2020 ◽  
pp. 014556132091062
Author(s):  
Yongli Zhang ◽  
Qi Tang ◽  
Ruoyan Xue ◽  
Xiaohui Zhu ◽  
Hua Yang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Family Members ◽  
Autosomal Dominant Inheritance ◽  
Dominant Inheritance ◽  
Genetic Characteristics ◽  
Whole Exome ◽  
The Family

Background: Otosclerosis is a focal lesion of the inner ear. The role of genetic factors in the pathogenesis of otosclerosis has received increasing attention. We analyzed the clinical manifestations, inheritance pattern, and pathogenic genes in a family with otosclerosis. Methods: We collected clinical data and generated a family pedigree. High-throughput second-generation sequencing technology was used to identify candidate genes by performing whole-exome sequencing of 7 members of the family, and Sanger sequencing was performed to validate candidate gene mutations in the 7 family members. Results: Otosclerosis was characterized by autosomal dominant inheritance in this family. Whole-exome sequencing did not reveal mutation sites in known deafness-related genes. However, a c.2209A > G (p.T737A) mutation was detected in exon 6 of the SP1 gene, which is associated with the COL1A1 gene. This mutation was a pathogenic mutation, and Sanger sequencing confirmed that this mutation cosegregated with the clinical phenotype among the family members. Conclusions: The pattern of otosclerosis in this family is consistent with autosomal dominant inheritance, and the SP1 gene, harboring the c.2209A > G (p.T737A) mutation in exon 6, may be the causative gene of otosclerosis in this family.

scholarly journals In silico analysis ofIDH3Agene revealed Novel mutations associated with Retinitis Pigmentosa

2019 ◽  
Author(s):  
Thwayba A. Mahmoud ◽  
Abdelrahman H. Abdelmoneim ◽  
Naseem S. Murshed ◽  
Zainab O. Mohammed ◽  
Dina T. Ahmed ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
In Silico ◽  
In Silico Analysis ◽  
Photoreceptor Cells ◽  
Structure And Function ◽  
Novel Mutations ◽  
Inherited Disorders ◽  
Bioinformatics Tools ◽  
And Function ◽  
Silico Analysis

AbstractBackgroundRetinitis Pigmentosa (RP) refers to a group of inherited disorders characterized by the death of photoreceptor cells leading to blindness. The aim of this study is to identify the pathogenic SNPs in the IDH3A gene and their effect on the structure and function of the protein.Methodwe used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein.Result20 deleterious SNPs out of 178 were found to have a damaging effect on the protein structure and function.Conclusionthis is the first in silico analysis of IDH3A gene and 20 novel mutations were found using different bioinformatics tools, and they could be used as diagnostic markers for Retinitis Pigmentosa.

scholarly journals Novel Mutations in GPR68 and SLC24A4 Cause Hypomaturation Amelogenesis Imperfecta

2021 ◽  
Vol 12 (1) ◽  
pp. 13
Author(s):  
Figen Seymen ◽  
Hong Zhang ◽  
Yelda Kasimoglu ◽  
Mine Koruyucu ◽  
James P. Simmer ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Frameshift Mutation ◽  
Tooth Enamel ◽  
Bioinformatic Analysis ◽  
Amelogenesis Imperfecta ◽  
Genetic Condition ◽  
Novel Mutations ◽  
Whole Exome ◽  
Homozygous Nonsense Mutation

Amelogenesis imperfecta (AI) is a rare genetic condition affecting the quantity and/or quality of tooth enamel. Hypomaturation AI is characterized by brownish-yellow discoloration with increased opacity and poorly mineralized enamel prone to fracture and attrition. We recruited three families affected by hypomaturation AI and performed whole exome sequencing with selected individuals in each family. Bioinformatic analysis and Sanger sequencing identified and confirmed mutations and segregation in the families. Family 1 had a novel homozygous frameshift mutation in GPR68 gene (NM_003485.3:c.78_83delinsC, p.(Val27Cysfs*146)). Family 2 had a novel homozygous nonsense mutation in SLC24A4 gene (NM_153646.4:c.613C>T, NP_705932.2:p.(Arg205*)). Family 3 also had a homozygous missense mutation in SLC24A4 gene which was reported previously (c.437C>T, p.(Ala146Val)). This report not only expands the mutational spectrum of the AI-causing genes but also improves our understanding of normal and pathologic amelogenesis.

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