scholarly journals Identification of a Novel KRT9 Frameshift Mutation in a Chinese Pedigree with Epidermolytic Palmoplantar Keratoderma

2021 ◽  
Vol 21 (04) ◽  
Author(s):  
Anli Shu
Keyword(s):  
Amino Acids ◽  
Linkage Analysis ◽  
Autosomal Dominant ◽  
Frameshift Mutation ◽  
Direct Sequencing ◽  
The Novel ◽  
Palmoplantar Keratoderma ◽  
Causative Gene ◽  
Responsible Gene ◽  
The Family

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant genodermatosis caused by variants of keratin 9 (KRT9) or KRT1 gene. In this study causative gene mapping in a Chinese EPPK family was performed with Two-point linkage analysis and haplotyping. Positive linkage results were obtained on 17q (Zmax=2.06, θmax=0.0) at D17S799, which indicated KRT9 to be the most responsible gene for the family. Subsequently, direct sequencing identified a novel frameshift mutation caused by a 5bp deletion (∆GGAGG) in KRT9 in all affected individuals but not in the unaffected members or the 50 unrelated controls. The frameshift changed the encoding of the following nine amino acids and resulted in a readthrough translation in exon 7. The data revealed that the novel frameshift mutation in KRT9 was responsible for the Chinese EPPK pedigree. The researchers’ findings broaden the spectrum of KRT9 variants and provide further evidence for the highly genetic heterogeneity of EPPK.

scholarly journals Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel mutation in arginine-vasopressin gene in a Brazilian family

2008 ◽  
Vol 52 (8) ◽  
pp. 1272-1276 ◽  
Author(s):  
Maria Edna de Melo ◽  
Suemi Marui ◽  
Vinícius Nahime de Brito ◽  
Marcio Corrêa Mancini ◽  
Berenice B. Mendonca ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Direct Sequencing ◽  
Sequencing Analysis ◽  
The Novel ◽  
Autosomal Dominant Disorder ◽  
Vasopressin Gene ◽  
Avp Gene

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare autosomal dominant disorder characterized by polyuria and polydipsia due to deficiency of arginine vasopressin (AVP). More than 50 mutations causing adFNDI have been already reported in the AVP gene. The aim of the present study is to analyze the AVP gene in four generations of one Brazilian kindred with adFNDI. The proband was a 31-year old female with huge hypotonic polyuria (10 L/day) dated from childhood. Molecular analysis included amplification of all exons and exon-intron regions of the AVP gene by PCR and direct sequencing. Sequencing analysis showed a novel point mutation in heterozygous: G88V (GGC>GTC). All affected patients presented the same mutation also in heterozygous, while it was absent in four normal members. We expand the repertoire of mutations in AVP describing the novel G88V mutation in one Brazilian kindred with adFNDI.

scholarly journals Novel mutations of PKD1 gene in Chinese patients with autosomal dominant polycystic kidney disease

2002 ◽  
Vol 17 (1) ◽  
pp. 75-80 ◽  
Author(s):  
Lan Ding ◽  
Sizhong Zhang ◽  
Weimin Qiu ◽  
Cuiying Xiao ◽  
Shaoqing Wu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Frameshift Mutation ◽  
Chinese Patients ◽  
Common Disease ◽  
Polycystic Kidney ◽  
Pkd1 Gene ◽  
Autosomal Dominant Polycystic Kidney

Abstract Background. Autosomal dominant polycystic kidney disease (ADPKD) is a common disease in China. The major gene responsible for ADPKD, PKD1, has been fully characterized and shown to encode an integral membrane protein, polycystin 1, which is thought to be involved in cell–cell and cell–matrix interaction. Until now, 82 mutations of PKD1 gene have been reported in European, American, and Asian populations. However, there has been no report on mutations of the PKD1 gene in a Chinese population. Methods. Eighty Chinese patients in 60 families with ADPKD were screened for mutations in the 3′ region of the PKD1 gene using polymerase chain reaction–single-strand conformation polymorphism (PCR–SSCP) and DNA-sequencing techniques. Results. Three mutations were found. The first mutation is a 12593delA frameshift mutation in exon 45, and the polycystin change is 4129WfsX4197, 107 amino acids shorter than the normal polycystin (4302aa). The second mutation is a 12470InsA frameshift mutation in exon 45, producing 4088DfsX4156, and the predicted protein is 148 amino acids shorter than the normal. The third one is a 11151C→T transition in exon 37 converting Pro3648 to Leu. In addition, nine DNA variants, including IVS44delG, were identified. Conclusions. Three mutations in Chinese ADPKD patients are described and all of them are de novo mutations. Data obtained from mutation analysis also suggests that the mutation rate of the 3′ single-copy region of PKD1 in Chinese ADPKD patients is very low, and there are no mutation hot spots in the PKD1 gene. Mutations found in Chinese ADPKD patients, including nucleotide substitution and minor frameshift, are similar to the findings reported by other researchers. Many mutations of the PKD1 gene probably exist in the duplicated region, promoter region, and the introns of PKD1.

scholarly journals Mutation detection and prenatal diagnosis of XLHED pedigree

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3691 ◽  
Author(s):  
Yao Lin ◽  
Wei Yin ◽  
Zhuan Bian
Keyword(s):  
Prenatal Diagnosis ◽  
Structural Changes ◽  
Frameshift Mutation ◽  
Stop Codon ◽  
Direct Sequencing ◽  
Premature Stop Codon ◽  
Deciduous Teeth ◽  
Chinese Family ◽  
Female Carrier ◽  
Causative Gene

Background The phenotypic characters of X -linked Hypohidrotic Ectodermal Dysplasia (XLHED) are the dysplasia of epithelial- and mesenchymal-derived organs. Ectodysplasin (EDA) is the causative gene of XLHED. Methods The current study reported a large Chinese XLHED pedigree. The genomic DNA of adult and fetus was extracted from peripheral blood and shed chorion cell respectively. The nucleotide variation in EDA gene was screened through direct sequencing the coding sequence. The methylation state of EDA gene’s promoter was evaluated by pyrosequencing. Results This Chinese XLHED family had two male patients and three carriers. All of them were with a novel EDA frameshift mutation. The mutation, c.172-173insGG, which leads to an immediate premature stop codon in exon one caused severe structural changes of EDA. Prenatal diagnosis suggested that the fetus was a female carrier. The follow-up observation of this child indicated that she had mild hypodontia of deciduous teeth at age six. The methylation level of EDA gene’s promoter was not related to carriers’ phenotype changes in this family. Discussion We reported a new frameshift mutation of EDA gene in a Chinese family. Prenatal diagnosis can help to predict the disease status of the fetus.

scholarly journals Case Report: Exome Sequencing Identified a Novel Frameshift Mutation of α-Actin 1 in a Chinese Family With Macrothrombocytopenia and Mild Bleeding

2021 ◽  
Vol 9 ◽  
Author(s):  
Fang-Mei Luo ◽  
Liang-Liang Fan ◽  
Yue Sheng ◽  
Yi Dong ◽  
Lv Liu
Keyword(s):  
Frameshift Mutation ◽  
Novel Mutation ◽  
Chinese Family ◽  
The Novel ◽  
Data Filtering ◽  
Public Database ◽  
The Public ◽  
Genetic Lesion ◽  
Gingival Bleeding ◽  
The Family

Inherited macrothrombocytopenia (IMTP) is a rare disorder characterized by a reduced platelet count and abnormally large platelets. The main clinical symptom of IMTP is mild bleeding in some patients. At present, more than 30 genes have been identified in patients with syndromic and non-syndromic IMTP. In this study, a 3-year-old boy and his mother who presented with mild epistaxis and/or gingival bleeding were diagnosed as having IMTP. Wen then selected whole sequencing to explore the genetic lesion of the patients. After data filtering and mutation validation, a novel frameshift mutation (NM_001130004: c.398_399insTGCG, p.F134AfsX60) of α-actin 1 (ACTN1) was identified in the proband and his mother but absent in other unaffected individuals. Previous studies have proven that mutations in ACTN1 may lead to IMTP with mild to absent bleeding phenotype. The novel mutation, resulting in a truncated protein in exon 4 of the ACTN1 gene, was absent in the public database, such as 1000G and genomAD. Further Western blot revealed that the expression of α-actin 1 in the proband was decreased overtly, which indicated that the novel frameshift mutation may induce non-sense-mediated mRNA decay. In summary, this study not only broadened the variants spectrum of ACTN1 gene, which may contribute to the genetic counseling of IMTP, but also confirmed the diagnosis of IMTP, which may help the management and prognosis for the family members.

scholarly journals Case Report: Identification of a Novel Pathogenic Germline TP53 Variant in a Family With Li–Fraumeni Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesco Paduano ◽  
Fernanda Fabiani ◽  
Emma Colao ◽  
Francesco Trapasso ◽  
Nicola Perrotti ◽  
...  
Keyword(s):  
Case Report ◽  
Autosomal Dominant ◽  
Liver Carcinoma ◽  
The Novel ◽  
Li Fraumeni Syndrome ◽  
Pathogenic Variants ◽  
Family Pedigree ◽  
The Family ◽  
Dominant Disease ◽  
Li Fraumeni

Li–Fraumeni syndrome (LFS) is an inherited autosomal dominant disease characterized by a predisposition to many cancers. Germline pathogenic variants in TP53 are primarily responsible for LFS. By performing a targeted sequencing panel in a proband with liver carcinoma having a deceased son affected by osteosarcoma, we found the novel heterozygous frameshift variant c.645del (p.Ser215Argfs*32) in the TP53 gene. This variant co-segregated with typical LFS cancers in the family pedigree, consistent with the pathogenicity of this novel and previously undescribed TP53 variant.

Novel, Aberrantly Truncated Isoform of Serum CD13 in a Family with High Serum Aminopeptidase N (CD13) Activity

2001 ◽  
Vol 47 (2) ◽  
pp. 223-230 ◽  
Author(s):  
Makoto Kawai ◽  
Yukichi Hara ◽  
Itsuro Miyazato ◽  
Seijin Hosaki
Keyword(s):  
Amino Acids ◽  
Healthy Volunteers ◽  
Direct Sequencing ◽  
High Serum ◽  
Aminopeptidase N ◽  
Reverse Transcription Pcr ◽  
The Family ◽  
Paternal Grandmother ◽  
Terminal Amino ◽  
Serum Aminopeptidase

Abstract Background: We previously reported a family in which the propositus and both her father and paternal grandmother had high serum aminopeptidase N (CD13; EC 3.4.11.2) activity (autosomal dominant). The molecular mass of the serum CD13 polypeptide of the propositus was larger than that of normal CD13, suggesting either a mutation in the CD13 gene or an abnormality in posttranslational modification of CD13 polypeptide in this family. Methods: Reverse transcription-PCR and direct sequencing were performed with leukocyte CD13 mRNA from the propositus. Two-dimensional electrophoresis and N-terminal amino acid sequencing were performed with serum CD13 from the propositus, the father of the propositus, and healthy volunteers. Results: The sequence of the CD13 cDNA of the propositus was essentially identical with that reported previously. However, the CD13 polypeptide of the propositus and the father of the propositus was truncated, lacking amino acids 1–43 of intact CD13 (43-truncated CD13), whereas CD13 lacking residues 1–58 (58-truncated CD13) and 43-truncated CD13 were detected in serum from healthy volunteers. Conclusions: In serum from healthy volunteers, we found both 58-truncated CD13, a major isoform reported previously, and 43-truncated CD13, a novel, minor isoform with a larger polypeptide. In serum of the family, 43-truncated CD13 was extremely concentrated, suggesting that proteolytic cleavage of CD13 amino acids 43 and 44 (43-truncation) is abnormally promoted. Because no mutation was found in the CD13 cDNA from the propositus, increased serum CD13 in this family seems to be caused by a mutation in a gene that regulates 43-truncation protease activity.

scholarly journals Roles of lysosomotropic agents on LRRK2 activation and Rab10 phosphorylation

2020 ◽  
Author(s):  
Tomoki Kuwahara ◽  
Kai Funakawa ◽  
Tadayuki Komori ◽  
Maria Sakurai ◽  
Gen Yoshii ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Autosomal Dominant ◽  
Rab Gtpases ◽  
The Novel ◽  
Causative Gene ◽  
Drug Induced ◽  
Extracellular Release ◽  
Enzymatic Activation ◽  
Lrrk2 Kinase ◽  
Lrrk2 Kinase Activity

AbstractLeucine-rich repeat kinase 2 (LRRK2), the major causative gene product of autosomal-dominant Parkinson’s disease, is a protein kinase that phosphorylates a subset of Rab GTPases. Since pathogenic LRRK2 mutations increase its ability to phosphorylate Rab GTPases, elucidating the mechanisms of how Rab phosphorylation is regulated by LRRK2 is of great importance. We have previously reported that chloroquine-induced lysosomal stress facilitates LRRK2 phosphorylation of Rab10 to maintain lysosomal homeostasis. Here we reveal that Rab10 phosphorylation by LRRK2 is potently stimulated by treatment of cells with a set of lysosome stressors and clinically used lysosomotropic drugs. These agents commonly promoted the formation of LRRK2-coated enlarged lysosomes and extracellular release of lysosomal enzyme cathepsin B, the latter being dependent on LRRK2 kinase activity. In contrast to the increase in Rab10 phosphorylation, treatment with lysosomotropic drugs did not increase the enzymatic activity of LRRK2, as monitored by its autophosphorylation at Ser1292 residue, but rather enhanced the molecular proximity between LRRK2 and its substrate Rab GTPases on the cytosolic surface of lysosomes. Lysosomotropic drug-induced upregulation of Rab10 phosphorylation was likely a downstream event of Rab29 (Rab7L1)-mediated enzymatic activation of LRRK2. These results suggest a regulated process of Rab10 phosphorylation by LRRK2 that is associated with lysosomal overload stress, and provide insights into the novel strategies to halt the aberrant upregulation of LRRK2 kinase activity.

scholarly journals Sporadic Progressive Symmetric Erythrokeratoderma: Classical Presentation of a rare Condition

2019 ◽  
Vol 17 (1) ◽  
pp. 69-72
Author(s):  
Kompal Agarwal ◽  
Sudha Agrawal ◽  
Anju Pradhan
Keyword(s):  
Early Childhood ◽  
Rare Disease ◽  
Autosomal Dominant ◽  
Rare Condition ◽  
Palmoplantar Keratoderma ◽  
The Family ◽  
The Face ◽  
History Of ◽  
Erythematous Plaques ◽  
Systemic Abnormality

Progressive symmetrical erythrokeratodermia (PSEK) is a rare autosomal dominant genodermatosis presenting in infancy or early childhood. An 11-year-old male presented with a history of pruritic, erythematous, scaly, hyperkeratotic plaques first noted at 5 years of age, with no history of similar lesions in the family. Cutaneous examination revealed multiple, irregularly shaped, erythematous plaques with fine, shiny white, adherent scaling distributed symmetrically over the face, trunk, inguinal area, bilateral axillae and extensor surfaces of limbs. Palmoplantar keratoderma was present with thickened, yellowish discolored nails. No systemic abnormality was found. The histopathological findings were consistent with PSEK. The case is being reported to increase the awareness about this rare disease.

SISTEM SOSIAL ALA NIKLASH LUHMAN DALAM NOVEL SEPERTIGA MALAM DI MANHATTAN KARYA ARUMI E

2019 ◽  
Vol 7 (2) ◽  
pp. 49
Author(s):  
Anton Wahyudi
Keyword(s):  
Social System ◽  
System Approach ◽  
Research Method ◽  
Qualitative Method ◽  
The Novel ◽  
Original Culture ◽  
The Family ◽  
Data Source ◽  
Social System Approach ◽  
Fictional Story

The novel Sepertiga Malam di Manhattan by Arumi E is very interesting to study. This novel is a novel about the struggle of a family to get happiness. This novel is the Arumi E's 27th newest novel. The struggle in this novel is to make the family happy, expecting for the baby. Before writing the novel, Arumi E did a research in the places written in the novel to achieve a very interesting fictional story and most of this story was taken from the traveling results so it was so interesting. The objective of this research is to describe (1) the Autopoetic System in the novel Sepertiga MalamdiManhattan by Arumi E. (2) The differentiation system in the Novel Sepertiga Malamdi Manhattan by Arumi E.The research method used is in the form of a descriptive qualitative method that uses a social system approach. The method used by the researcher is the dialectical method. The data source used in this research is the novel Sepertiga Malamdi Manhattan by Arumi E, published by Gramedia publisher in 2018. The data collection in this study uses the steps of reading the novel. To collect data, the researcher use any instrument.There are two results of the study: (1) The autopoetic system in the novel Sepertiga MalamdiManhattan by Arumi E. is concerning to some characters who have their own beliefs or rules in their lives who do not want to follow the rules of others, they are more confident in their own way to success and purpose of life. (2) The system of differentiation in the novel Sepertiga Malamdi Manhattan by Arumi E. is covering the handling of changes in the environment, the characters are able to adapt to the new environment, which has a different culture from the original culture. This shows evidence of the system autopoetic and differentiation in the novel Sepertiga MalamdiManhattan by Arumi E.

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