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.

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 Novel ARG1 variants identified in a patient with arginase 1 deficiency

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Katsuyuki Yokoi ◽  
Yoko Nakajima ◽  
Toshihiro Yasui ◽  
Makoto Yoshino ◽  
Tetsushi Yoshikawa ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Arginase Activity ◽  
Compound Heterozygous ◽  
Measurement Sensitivity ◽  
Protein Core ◽  
Arginase 1 ◽  
Conserved Domain ◽  
New Variant ◽  
Compound Heterozygous Variants

AbstractWe report a case of a 13-year-old boy with arginase 1 deficiency carrying a new variant in ARG1. Sanger sequencing identified the compound heterozygous variants: NM_000045.4: c.365G>A (p.Trp122*)/c.820G>A (p.Asp274Asn). Although not previously reported, the p.Asp274Asn variant is predicted to have strong pathogenicity because it is located in a highly conserved domain in the protein core and arginase activity in the patient was below measurement sensitivity.

Identification of Two Novel Mutations in PKHD1 Gene from Two Families with Polycystic Kidney Disease by Whole Exome Sequencing

2021 ◽  
Vol 22 ◽  
Author(s):  
Masoud Heidari ◽  
Hamid Gharshasbi ◽  
Alireza Isazadeh ◽  
Morteza Soleyman-Nejad ◽  
Mohammad Hossein Taskhiri ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Exome Sequencing ◽  
Polycystic Kidney Disease ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Genetic Alterations ◽  
Polycystic Kidney ◽  
Novel Mutations ◽  
Whole Exome

Background:: Polycystic kidney disease (PKD) is an autosomal recessive disorder resulting from mutations in the PKHD1 gene on chromosome 6 (6p12), a large gene spanning 470 kb of genomic DNA. Objective: The aim of the present study was to report newly identified mutations in the PKHD1 gene in two Iranian families with PKD. Materials and Methods: Genetic alterations of a 3-month-old boy and a 27-year-old girl with PKD were evaluated using whole-exome sequencing. The PCR direct sequencing was performed to analyse the co-segregation of the variants with the disease in the family. Finally, the molecular function of the identified novel mutations was evaluated by in silico study. Results: In the 3 month-old boy, a novel homozygous frameshift mutation was detected in the PKHD1 gene, which can cause PKD. Moreover, we identified three novel heterozygous missense mutations in ATIC, VPS13B, and TP53RK genes. In the 27-year-old woman, with two recurrent abortions history and two infant mortalities at early weeks due to metabolic and/or renal disease, we detected a novel missense mutation on PKHD1 gene and a novel mutation in ETFDH gene. Conclusion: In general, we have identified two novel mutations in the PKHD1 gene. These molecular findings can help accurately correlate genotype and phenotype in families with such disease in order to reduce patient births through preoperative genetic diagnosis or better management of disorders.

Ty1 in vitro integration: effects of mutations in cis and in trans

1994 ◽  
Vol 14 (9) ◽  
pp. 5731-5740
Author(s):  
L T Braiterman ◽  
J D Boeke
Keyword(s):  
Missense Mutation ◽  
Frameshift Mutations ◽  
Amino Terminal ◽  
Dna Molecule ◽  
Conserved Domain ◽  
In Trans ◽  
In Cis ◽  
Obvious Similarity ◽  
Insertion Mutations

Mutations within the TYB gene of Ty1 encoding integrase (IN) as well as alterations in its substrate, a linear DNA molecule, were examined for their effects on in vitro IN activity, using a recently developed physical assay. Five different codon-insertion mutations, two frameshift mutations, and one missense mutation, previously identified as transposition-deficient mutations, were tested. Virus-like particles, the source of IN, from two different protease mutants and a reverse transcriptase mutant exhibited near-normal to normal IN activity. Two frameshift mutations mapping within the phylogenetically variable C-terminal domain of IN resulted in significant in vitro IN activity. In contrast, three mutations within the amino-terminal conserved domain of IN completely abolished IN activity. When the substrate termini were mutated, we found that substrates with as few as 4 bp of Ty1 termini were capable of efficiently generating integration products. Surprisingly, certain substrates that lacked obvious similarity to Ty1 termini were also readily integrated into both linear and circular targets, whereas others were not used as substrates at all. Termini rich in adenosine residues were among the more active substrates; however, certain substrates lacking terminal adenosine residues can form small quantities of integration products, including complete integration reactions.

Two novel mutations in gene SPG4 in patients with autosomal dominant spastic paraplegia

2016 ◽  
Vol 52 (6) ◽  
pp. 603-607 ◽  
Author(s):  
A. F. Akhmetgaleyeva ◽  
I. M. Khidiyatova ◽  
E. V. Saifullina ◽  
R. F. Idrisova ◽  
R. V. Magzhanov ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Spastic Paraplegia ◽  
Novel Mutations

scholarly journals Mutations in NOTCH3 Gene may Promote the Clinical Presentation of Spinocerebellar Ataxia Type 37 Caused by Mutations in DAB1 Gene

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhao-Wei Wang ◽  
Li-Ping Wang ◽  
Ye Du ◽  
Qi Liu
Keyword(s):  
Spinocerebellar Ataxia ◽  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Bioinformatics Analysis ◽  
Clinical Presentation ◽  
Cerebellar Atrophy ◽  
Gene Mutations ◽  
Brain Magnetic Resonance Imaging ◽  
Diagnostic Methods ◽  
Spinocerebellar Ataxia Type

Background: Autosomal dominant spinocerebellar ataxia type 37 (SCA37) and Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) result from DAB1 and NOTCH3 gene mutations, respectively.Methods: In addition to conventional diagnostic methods, next-generation sequencing (NGS) and Sanger sequencing were performed to define and confirm the DAB1 and NOTCH3 gene mutation for a Chinese pedigree. Bioinformatics analysis was also applied for the mutated DAB1 and NOTCH3 protein using available software tools.Results: Brain magnetic resonance imaging shows diffuse leukoencephalopathy and cerebellar atrophy in the proband. NGS and Sanger sequencing identified two novel heterozygous mutations: NM_021080:c.318T &gt; G (p.H106Q) in the DAB1 gene and NM_000435:c.3298C &gt; T (p.R1100C) in the NOTCH3 gene. Bioinformatics analysis suggested that the DAB1 and NOTCH3 gene mutations are disease-causing and may be responsible for the phenotypes.Conclusion: This is the first report of a pedigree with both SAC37 and CADASIL phenotypes carrying corresponding gene mutations. Mutations in the NOTCH3 gene may promote the clinical presentation of spinocerebellar ataxia type 37 caused by mutations in the DAB1 gene. In addition to general examinations, it is vital for physicians to apply molecular genetics to get an accurate diagnosis in the clinic, especially for rare diseases.

Genetic diagnosis of Hailey–Hailey disease in two Chinese families: novel mutations in theATP2C1gene

2009 ◽  
Vol 34 (8) ◽  
pp. e968-e971 ◽  
Author(s):  
Y. G. Ding ◽  
H. Fang ◽  
L. M. Lao ◽  
X. J. Jiang ◽  
H. C. Chen
Keyword(s):  
Genetic Diagnosis ◽  
Novel Mutations ◽  
Chinese Families
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