scholarly journals A Frameshift Variant in KIAA0825 Causes Postaxial Polydactyly

2020 ◽  
pp. 1-5
Author(s):  
Muhammad Bilal ◽  
Wasim Ahmad
Keyword(s):  
Stop Codon ◽  
Premature Stop Codon ◽  
Causative Gene ◽  
Pakistani Population ◽  
Postaxial Polydactyly ◽  
The Family ◽  
Novel Variant ◽  
Limb Malformations ◽  
Polymorphic Microsatellite ◽  
Autosomal Recessive Manner

Postaxial polydactyly (PAP) is characterized by counterproductive 5th digit (pinky finger) duplication on hands and/or feet which often leads to functional complications. To date, at least 11 genes involved in causing various types of nonsyndromic polydactylies have been reported. In the present study, a consanguineous family of Sindhi origin with a segregating nonsyndromic form of PAP in an autosomal recessive manner was clinically and genetically evaluated. Genotyping, using polymorphic microsatellite markers, established linkage in the family on chromosome 5q15 harboring the <i>KIAA0825</i> gene (MIM 617266). Sequence analysis of the gene revealed a novel frameshift variant leading to a premature stop codon [c.143delG, p.(Cys48Serfs*28)]. This is only the 4th novel variant in the <i>KIAA0825</i> gene that leads to PAP type A10 (PAPA10) (MIM 618498). Identification of variants in the PAP causative gene will support the diagnosis of patients with limb malformations in the Pakistani population.

scholarly journals Family’s History Based on the CDH1 Germline Variant (c.360delG) and a Suspected Hereditary Gastric Cancer Form

2020 ◽  
Vol 21 (14) ◽  
pp. 4904
Author(s):  
Laura Caggiari ◽  
Mara Fornasarig ◽  
Mariangela De Zorzi ◽  
Renato Cannizzaro ◽  
Agostino Steffan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Susceptibility ◽  
Stop Codon ◽  
Case Reports ◽  
Premature Stop Codon ◽  
Diffuse Gastric Cancer ◽  
Cancer Syndrome ◽  
The Family ◽  
Hereditary Gastric Cancer ◽  
E Cadherin

Hereditary diffuse gastric cancer (HDGC) is a cancer susceptibility syndrome caused by germline pathogenic variant in CDH1, the gene encoding E-cadherin. The germline loss-of-function variants are the only proven cause of the cancer syndrome HDGC, occurring in approximately 10–18% of cases and representing a helpful tool in genetic counseling. The current case reports the family history based on a CDH1 gene variant, c.360delG, p.His121Thr in a suspected family for hereditary gastric cancer form. This frameshift deletion generates a premature stop codon at the amino acid 214, which leads to a truncated E-cadherin protein detecting it as a deleterious variant. The present study expands the mutational spectra of the family with the CDH1 variant. Our results highlight the clinical impact of the reported CDH1 variant running in gastric cancer families.

scholarly journals A new mutation at exon 2 of hprt1 locus causing Lesch-Nyhan Syndrome.

2015 ◽  
Vol 3 (1) ◽  
pp. 18-21
Author(s):  
Adriana María Gil Zapata ◽  
Adriana Castillo Pico ◽  
Leonor Gusmão ◽  
António Amorim ◽  
Fernando Rodríguez Sanabria
Keyword(s):  
Genetic Counseling ◽  
Inborn Error ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Dna Fragments ◽  
Hprt Gene ◽  
New Mutation ◽  
Exon 2 ◽  
The Family ◽  
Hypoxanthine Guanine Phosphoribosyl Transferase

Introduction: Lesch-Nyhan síndrome (LNS) is an X-linked recessive inborn error of metabolism, due to deficiency of the enzyme Hypoxanthine-guanine-phosphoribosyl transferase (HGPRT; EC.2.4.2.8) resulting in hyperuricemia, neurological and behavioural disturbances. In the present work, we report the results of the study of a Colombian family, where LNS was previously clinically and biochemically diagnosed. Material and Methods: The full HPRT gene, including 9 exons and 8 introns, was amplified on eight separate DNA fragments. Both strands, forward and reverse, of the amplified DNA fragments were analyzed and the obtained sequences were compared with those deposited at National Center for Biotechnology Information. Results and conclusions: Sequence analysis allowed the detection of new LNS causing mutation, an adenine deletion in exon 2 of HPRT1 gene resulting in a frameshift which determines a premature stop codon. This study, besides adding a new mutation to the already large spectrum of disease causing variation at HPRT, allows therefore providing genetic counseling for the family as well as prenatal diagnosis.

scholarly journals Intronic splicing of hyaluronan synthase 1 (HAS1): a biologically relevant indicator of poor outcome in multiple myeloma

Blood ◽  
2005 ◽  
Vol 105 (12) ◽  
pp. 4836-4844 ◽  
Author(s):  
Sophia Adamia ◽  
Tony Reiman ◽  
Mary Crainie ◽  
Michael J. Mant ◽  
Andrew R. Belch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Splice Variants ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Hyaluronan Synthase ◽  
Gene Splicing ◽  
Biologically Relevant ◽  
Mitotic Abnormalities ◽  
The Family

Abstract In this study, we show that the hyaluronan synthase 1 (HAS1) gene undergoes aberrant intronic splicing in multiple myeloma (MM). In addition to HAS1 full length (HAS1FL), we identify 3 novel splice variants of HAS1, HAS1Va, HAS1Vb, and HAS1Vc, detected in patients with MM or monoclonal gammopathy of undetermined significance (MGUS). HAS1Vb and HAS1Vc undergo intronic splicing with creation of a premature stop codon. MM cells expressing one or more HAS1 variants synthesize extracellular and/or intracellular hyaluronan (HA). Expression of the HAS1Vb splice variant was significantly correlated with reduced survival (P = .001). Together, alternative HAS1 gene splicing, the correlations between HAS1 splicing and HA synthesis, and the correlations between HAS1 splicing and reduced survival of MM patients support the hypothesis that the family of HAS1 protein plays a significant role in disease progression. Further, expression of HAS1Vb, in conjunction with HAS1FL and/or other HAS1 variants, may lead to accumulation of intracellular HA molecules and an impact on receptor for HA-mediated motility (RHAMM)-mediated mitotic abnormalities in MM. This study highlights the potential importance of HAS1 and its alternative splicing in pathophysiology of MGUS and MM. (Blood. 2005;105: 4836-4844)

scholarly journals Autosomal Recessive Oculodentodigital Dysplasia: A Case Report and Review of the Literature

2018 ◽  
Vol 154 (4) ◽  
pp. 181-186 ◽  
Author(s):  
Elifcan Taşdelen ◽  
Ceren D. Durmaz ◽  
Halil G. Karabulut
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Rare Condition ◽  
Clinical Findings ◽  
Homozygous Mutation ◽  
Nasal Bridge ◽  
Oculodentodigital Dysplasia ◽  
Autosomal Recessive Manner

Oculodentodigital dysplasia (ODDD) is a rare condition characterized by a typical facial appearance and variable findings of the eyes, teeth, and fingers. ODDD is caused by mutations in the GJA1 gene in chromosome 6q22 and inherited in an autosomal dominant manner in the majority of the patients. However, in recent clinical reports, autosomal recessive ODDD cases due to by GJA1 mutations were also described. Here, we report on a 14-year-old boy with microphthalmia, microcornea, narrow nasal bridge, hypoplastic alae nasi, prominent columnella, hypodontia, dental caries, and partial syndactyly of the 2nd and 3rd toes. These clinical findings were concordant with the diagnosis of ODDD, and a novel homozygous mutation (c.442C>T, p.Arg148Ter) was determined in the GJA1 gene leading to a premature stop codon. His phenotypically normal parents were found to be carriers of the same mutation. This is the third family in the literature in which ODDD segregates in an autosomal recessive manner.

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 Mutation in the RPE65 gene causing hereditary retinal dystrophy in the Briard dogs: application of a new detection method

2008 ◽  
Vol 53 (No. 4) ◽  
pp. 176-179
Author(s):  
R. Bechyňová ◽  
J. Dostál ◽  
A. Stratil ◽  
F. Jílek ◽  
P. Horák
Keyword(s):  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Stop Codon ◽  
Retinal Dystrophy ◽  
Premature Stop Codon ◽  
Causative Mutation ◽  
Functional Protein ◽  
Hereditary Retinal Dystrophy ◽  
Briard Dogs ◽  
Autosomal Recessive Manner

Inherited eye diseases are widespread in most of the pure dog breeds and they show a severe impact on canine health, welfare and working ability. Congenital stationary night blindness (CSNB) was originally described in Briards. CSNB is slow progressive retinal degeneration with very early onset of clinical symptoms and is inherited in an autosomal recessive manner. The causative mutation (Y16567.1:c.487_490delAAGA) for CSNB was identified in exon 5 of the <I>RPE6</I>5 gene. This deletion results in a frameshift and leads to a premature stop codon and expression of a non-functional protein. To date, only expensive, laborious or unpractical methods have been used for detection of the mutation in the canine <I>RPE65</I> gene. The main goals of this study were to develop a new method for routine genotyping of the causative mutation and to assess its occurrence in the Czech population of Briards. The method of electrophoresis in the gel Spraedex EL600 can be widely used for genotyping of the <I>RPE65</I> gene as a basis of proper genetic counselling and an improvement of genetic health in the Briard populations. In the studied population, the following frequencies of alleles + (wild) and – (mutant) were observed – 0.939 and 0.061, respectively.

scholarly journals A Premature Stop Codon in RAF1 Is the Priority Candidate Causative Mutation of the Inherited Chicken Wingless-2 Developmental Syndrome

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 353
Author(s):  
Ingrid Youngworth ◽  
Mary E. Delany
Keyword(s):  
Signaling Pathway ◽  
Limb Development ◽  
Cellular Proliferation ◽  
Stop Codon ◽  
Point Mutations ◽  
Premature Stop Codon ◽  
Mapk Signaling ◽  
Candidate Region ◽  
Causative Mutation ◽  
Causative Gene

The chicken wingless-2 (wg-2) mutation is inherited in an autosomal recessive fashion, and the resulting phenotype in mutant (wg-2/wg-2) individuals is a developmental syndrome characterized by absent wings, truncated legs, craniofacial as well as skin and feather defects, and kidney malformations. Mapping and genotyping established that the mutation resides within 227 kilobases (kb) of chromosome 12 in a wg-2 congenic inbred line. A capture array was designed to target and sequence the candidate region along with flanking DNA in 24 birds from the line. Many point mutations and insertions or deletions were identified, and analysis of the linked variants indicated a point mutation predicted to cause a premature stop codon in the RAF1 gene. Expression studies were conducted inclusive of all genes in the candidate region. Interestingly, RAF1 transcription was elevated, yet the protein was absent in the mutants relative to normal individuals. RAF1 encodes a protein integral to the Ras/Raf/MAPK signaling pathway controlling cellular proliferation, and notably, human RASopathies are developmental syndromes caused by germline mutations in genes of this pathway. Our work indicates RAF1 as the priority candidate causative gene for wg-2 and provides a new animal model to study an important signaling pathway implicated in limb development, as well as RASopathies.

scholarly journals Novel Variant of AVPR2 Giving Rise to X-Linked Congenital Nephrogenic Diabetes Insipidus in a 7-Month-Old Danish Boy

2020 ◽  
Vol 10 (3) ◽  
pp. 124-129
Author(s):  
Johanne Emy Sollid ◽  
Shivani Joshi ◽  
Malgorzata  Pulczynska Wason ◽  
Søren Rittig ◽  
Jane Hvarregaard Christensen ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Gene Encoding ◽  
Exon 2 ◽  
Congenital Nephrogenic Diabetes Insipidus ◽  
Novel Variant ◽  
Precise Diagnosis ◽  
The One

Patients affected with congenital nephrogenic diabetes insipidus (CNDI) have reduced ability to concentrate urine. Early diagnosis of CNDI is important to avoid recurrent episodes of severe dehydration. We present a Danish male suffering from typical symptoms and diagnosed with CNDI at the age of 7 months. Gene sequencing of this proband and his mother revealed a novel variant in the gene encoding the antidiuretic hormone receptor (<i>AVPR2</i>). The variant is a deletion of nucleotide c.151 in exon 2 of <i>AVPR2</i> (GenBank NM_000054.4:c.151del). This 1bp deletion is predicted to cause a frameshift that results in tryptophan replacing valine at position 51 in <i>AVPR2</i> and a premature stop codon three codons downstream (p.Val51Trpfs*3) likely resulting in faulty expression of the receptor. Identification of disease-causing variants such as the one described here contributes to precise diagnosis, especially in carriers and newborns, thus preventing the long-term physical and intellectual disability observed in some CNDI-patients.

scholarly journals Incomplete Segregation of MSH6 Frameshift Variants with Phenotype of Lynch Syndrome

2017 ◽  
Author(s):  
Raffaella Liccardo ◽  
Marina De Rosa ◽  
Giovanni Battista Rossi ◽  
Nicola Carlomagno ◽  
Paola Izzo ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
In Silico ◽  
Stop Codon ◽  
Direct Sequencing ◽  
Premature Stop Codon ◽  
In Silico Analysis ◽  
Frameshift Deletion ◽  
The Family ◽  
Novel Variants ◽  
Repair Genes

Background: Lynch syndrome, the most frequent form of hereditary colorectal cancer and involves mutations in mismatch repair genes. The aim of this study was to identify mutations in MSH6 from 97 subjects negative for mutations in MLH1 and MSH2. Methods: By direct sequencing, we identified 27 MSH6 variants, of which, nine were novel. To verify the pathogenicity of these novel variants we performed in silico and segregation analyses. Results: Three novel variants were predicted by in silico analysis as damaging mutations and segregated with the disease phenotype. While, a novel frameshift deletion variant that was predicted to yield a premature stop codon, did not segregate with the LS phenotype in 3 of 4 cases in the family. Interestingly, another frame-shift variant identified in this study, already described in the literature, also did not segregate with the LS phenotype in 1 of 2 affected subjects in the family. In all affected subjects of both families, no mutation was detected in other MMR genes. Therefore, it is expected that within these families other genetic factors contribute to the disease either alone or in combination with MSH6 variants. Conclusion: We conclude that caution should be exercised in counseling for MSH6-associated LS family members.

scholarly journals Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K

2012 ◽  
Vol 209 (3) ◽  
pp. 463-470 ◽  
Author(s):  
Mary Ellen Conley ◽  
A. Kerry Dobbs ◽  
Anita M. Quintana ◽  
Amma Bosompem ◽  
Yong-Dong Wang ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Normal Growth ◽  
Cell Development ◽  
Unknown Etiology ◽  
Causative Gene ◽  
Organ Systems

Whole exome sequencing was used to determine the causative gene in patients with B cell defects of unknown etiology. A homozygous premature stop codon in exon 6 of PIK3R1 was identified in a young woman with colitis and absent B cells. The mutation results in the absence of p85α but normal expression of the p50α and p55α regulatory subunits of PI3K. Bone marrow aspirates from the patient showed &lt;0.1% CD19+ B cells with normal percentages of TdT+VpreB+CD19− B cell precursors. This developmental block is earlier than that seen in patients with defects in the B cell receptor signaling pathway or in a strain of engineered mice with a similar defect in p85α. The number and function of the patient’s T cells were normal. However, Western blot showed markedly decreased p110δ, as well as absent p85α, in patient T cells, neutrophils, and dendritic cells. The patient had normal growth and development and normal fasting glucose and insulin. Mice with p85α deficiency have insulin hypersensitivity, defective platelet function, and abnormal mast cell development. In contrast, the absence of p85α in the patient results in an early and severe defect in B cell development but minimal findings in other organ systems.

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