A Novel ATM Gene Mutation Affecting Splicing in an Ataxia-Telangiectasia Patient

2021 ◽  
pp. 1-5
Author(s):  
Esra Arslan Ateş ◽  
Ayberk Türkyılmaz ◽  
Sevgi Bilgiç Eltan ◽  
Safa Barış ◽  
Ahmet Ilter Güney
Keyword(s):  
Ataxia Telangiectasia ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Acceptor Site ◽  
Nonsense Mediated Decay ◽  
Splicing Pattern ◽  
Progressive Ataxia ◽  
Nucleotide Insertion ◽  
Alternatively Spliced

Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by progressive ataxia, choreoathetosis and immunodeficiency beginning in early childhood. An 8-year-old girl was referred with a diagnosis of AT. She had gait disturbance and dysarthria for 3years. Multiple cutaneous telangiectases were observed on her face, trunk and limbs. Sequence analysis of the <i>ATM</i> gene revealed a homozygous c.7308–15A&#x3e;G mutation in IVS49. Human Splicing Finder predicted that the mutation could activate an intronic cryptic acceptor site. We designed primers for amplification of related exons (48–50) from cDNA for evaluating splicing pattern. Sequencing of <i>ATM</i> exons 48–50 revealed a 14-nucleotide insertion from intron 49, between exons 49 and 50, resulting in premature termination of translation at codon 2439. To conclude, we report a novel mutation in a classical AT case, which resulted in an alternatively spliced transcript and was predicted to form a truncated protein or null protein due to nonsense-mediated decay.

Novel Mutation in PLA2G6 Gene in a Patient with Infantile Neuroaxonal Dystrophy

2016 ◽  
Vol 15 (02) ◽  
pp. 073-075 ◽  
Author(s):  
Aravindhan Veerapandiyan ◽  
Amit Chaudhari ◽  
Akilandeswari Aravindhan ◽  
Caroline Hayes-Rosen
Keyword(s):  
Autosomal Recessive ◽  
Novel Mutation ◽  
Cerebellar Atrophy ◽  
Autosomal Recessive Disorder ◽  
Neuroaxonal Dystrophy ◽  
Infantile Neuroaxonal Dystrophy ◽  
Group Vi ◽  
Calcium Independent Phospholipase A2 ◽  
Bulbar Dysfunction ◽  
Spastic Quadriparesis

AbstractInfantile neuroaxonal dystrophy (INAD) is an autosomal recessive disorder that causes psychomotor regression. Clinicopathological features include truncal hypotonia followed by spastic quadriparesis, strabismus, nystagmus, cerebellar ataxia, bulbar dysfunction, and cerebellar atrophy. INAD is associated with a variety of mutations in the PLA2G6 gene that encodes the group VI calcium-independent phospholipase A2 protein which is important in cell membrane homeostasis. Defects in this protein cause axonal dystrophy. We report a 2-year-old boy with INAD who was found to have a novel deletion c.1019_1025del7 leading to a frame shift in the PLA2G6 gene. We suggest that this change may be an addition to the array of mutations causing INAD.

scholarly journals FRIEDREICH ATAXIA – A CASE REPORT

2014 ◽  
Vol 04 (02) ◽  
pp. 133-135
Author(s):  
Deepthi R. V. ◽  
Seema Pavanam ◽  
Vijaya Shenoy ◽  
Siddarth S. Joshi
Keyword(s):  
Autosomal Recessive ◽  
Trinucleotide Repeat ◽  
Friedreich Ataxia ◽  
Autosomal Recessive Disorder ◽  
Ataxic Gait ◽  
Progressive Ataxia ◽  
Extensor Plantar Response ◽  
Romberg Test ◽  
Endocrine Abnormality ◽  
Tendon Reflexes

Abstract:Friedreich ataxia is an autosomal recessive disorder, due to expansion of trinucleotide repeat in Frataxin gene which presents with ataxic gait, absent tendon reflexes, extensor plantar response and positive Romberg test. We present a child who came with complaints of progressive ataxia of gait since the age of 10 years and was diagnosed to have Friedreich ataxia. They have associated cardiomyopathy and endocrine abnormality like diabetes and hypothyroidism.

scholarly journals Diagnosis and Management of Ataxia-Telangiectasia in Resource-Limited Settings

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Nienke J.H. Van Os ◽  
Koen J Van Aerde ◽  
Judith Van Gaalen ◽  
Peter J Merkus ◽  
Laura Silveira-Moriyama ◽  
...  
Keyword(s):  
Ataxia Telangiectasia ◽  
Autosomal Recessive ◽  
Growth Failure ◽  
Autosomal Recessive Disorder ◽  
Resource Limited Settings ◽  
Diagnosis And Management ◽  
Complex Disorder ◽  
Resource Limited ◽  
Serum Alpha Fetoprotein ◽  
Atm Gene

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder linked to mutations in the ATM gene, and is characterized by neurodegeneration with an early onset cerebellar syndrome, hyperkinetic movement disorders, neuropathy, and oculocutaneous telangiectasia. Immunodeficiency, pulmonary disease, growth failure, diabetes mellitus, increased malignancy risk and hypersensitivity to ionizing radiation complicate the clinical picture. Serum alpha-fetoprotein levels are increased in patients with A-T and can therefore serve as a diagnostic marker for the disease. In resource-limited settings, diagnosis and management of patients with a rare and complex disorder such as A-T may be extremely challenging. This expert opinion-based guideline aims to give an overview of diagnosis and management of A-T in resource-limited settings, by prioritizing different options based on medical necessity, availability, and costs.

scholarly journals A Novel Mutation in the VPS13B Gene in a Cohen Syndrome Patient with Positive Antiphospholipid Antibodies

2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
Roghayeh Dehghan ◽  
Mahdiyeh Behnam ◽  
Alireza Moafi ◽  
Mansoor Salehi
Keyword(s):  
Antiphospholipid Antibodies ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Mental Deficiency ◽  
Autosomal Recessive Disorder ◽  
Facial Features ◽  
Loss Of Function ◽  
Cohen Syndrome ◽  
Mild Anemia ◽  
Homozygous Nonsense Mutation

Cohen syndrome is an autosomal recessive disorder with the primary symptoms of mental deficiency, progressive retinopathy, hypotonia, microcephaly, obesity of midchildhood onset, intermittent neutropenia, and dysmorphic facial features. The syndrome has high phenotypic heterogeneity and is caused by loss-of-function mutations in the VPS13B gene. Here, we introduce a novel homozygous nonsense mutation (c.8698G > T, p.E2900X) in the VPS13B gene in an 11-year-old Iranian boy with major symptoms of Cohen syndrome. He also had mild anemia accompanied by positive antiphospholipid antibodies, the latter has never been previously reported in Cohen syndrome.

scholarly journals Molecular Diagnosis of Analbuminemia: A Novel Mutation Identified in Two Amerindian and Two Turkish Families

2002 ◽  
Vol 48 (6) ◽  
pp. 844-849 ◽  
Author(s):  
Monica Galliano ◽  
Monica Campagnoli ◽  
Antonio Rossi ◽  
Carl Heinz Wirsing von König ◽  
Andrew W Lyon ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Heteroduplex Analysis ◽  
Translation Product ◽  
Amino Acid Residues ◽  
New Mutation ◽  
Single Strand Conformational Polymorphism ◽  
Turkish Origin ◽  
Albumin Gene

Abstract Background: Analbuminemia is a rare autosomal recessive disorder in which individuals have little or no circulating albumin, usually the most abundant plasma protein. We describe a new mutation associated with analbuminemia. Methods: We studied four apparently unrelated patients who had congenital analbuminemia: two of Amerindian and two of Turkish origin. The 14 exons and the flanking intron sequences of the albumin gene were amplified by PCR and screened for mutations by single-strand conformational polymorphism and heteroduplex analysis. The mutated DNA fragments were sequenced directly. Results: In all four cases, analbuminemia was caused by the same mutation, an AT deletion at nucleotides 2430–2431, the 91st and 92nd bases of exon 3. This novel defect, named Kayseri, produces a frameshift leading to a premature stop two codons downstream. The predicted translation product would consist of 54 amino acid residues. Conclusions: The AT deletion at nucleotides 2430–2431 is a novel mutation associated with analbuminemia.

THE KNOWN UK CASES OF ATAXIA TELANGIECTASIA-LIKE DISORDER (ATLD)

2015 ◽  
Vol 86 (11) ◽  
pp. e4.184-e4
Author(s):  
Katy Westwood ◽  
John Ealing ◽  
Malcolm Taylor ◽  
Paul Worth ◽  
Andrea Nemeth
Keyword(s):  
Ataxia Telangiectasia ◽  
Genome Stability ◽  
Autosomal Recessive ◽  
Atm Kinase ◽  
Clinical Presentations ◽  
Progressive Ataxia ◽  
Atm Gene ◽  
Spontaneous Chromosome ◽  
The Uk ◽  
Rare Autosomal Recessive Disease

Ataxia telangiectasia-like disorder (ATLD) is a very rare autosomal recessive disease with only 25 patients recognised worldwide. ATLD is likened to Ataxia telangiectasia (A-T) due to an overlap of clinical presentations and cellular characteristics. The clinical hallmark of A-T and ATLD is progressive young onset cerebellar ataxia. Variably present characteristics include dysarthria, oculomotor apraxia, ocular telangiectasia, immunodeficiency, spontaneous chromosome abnormalities and a predisposition to malignancy. In contrast to A-T, ocular telangiectasia is absent. Furthermore, ATLD patients tend to have a later onset and slower progression of neurological signs than A-T. The ATM gene, that has a key role in genome stability, is mutated in A-T resulting in an increase cancer predisposition. In ATLD, gene MRE11 is mutated leading to deficient activation of ATM. A functional consequence of the MRE11 mutation is raised chromosomal radiosensitivity because functional ATM kinase is required to rejoin chromosome breaks. This poster/presentation will describe the clinical features and genetic analysis of the ATLD cases with progressive ataxia known in the UK. Undergraduate Prize Winner 2015

scholarly journals A novel mutation in CYP17A1 gene leads to congenital adrenal hyperplasia: A case report

2019 ◽  
Author(s):  
Majid Nazari ◽  
Mohammad Yahya Vahidi Mehrjardi ◽  
Nosrat Neghab ◽  
Mahdi Aghabagheri ◽  
Nasrin Ghasemi
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Homozygous Deletion ◽  
Blood Levels ◽  
Primary Amenorrhea ◽  
Adrenal Hyperplasia ◽  
Lyase Deficiency

Background: Congenital adrenal hyperplasia is a rare autosomal recessive disorder where the mutation in P450 family 17 subfamily A member 1 gene (CYP17A1) is involved in its etiology. The disorder represents itself with low blood levels of estrogens, androgens, and cortisol that generally couples with hypertension, Hypokalemia, sexual primary amenorrhea, infantilism and in affected individuals. Case: In this study, the CYP17A1 gene in a 14-year-old female was examined. The karyotype of the patient was 46, XX, and the analysis of the CYP17A1 gene by Sanger sequencing revealed a novel homozygous deletion c.1052-1054CCT which led to isolated 17,20-lyase deficiency. Conclusion: In conclusion, this study report an in-frame deletion which results in isolated 17, 20-lyase deficiency, and the mutation might be used for diagnosis in other patients with distinctive clinical symptoms.

scholarly journals Two Novel Heterozygote Mutations of ATM in a Chinese Family with Dystonia-Dominant Ataxia Telangiectasia and Literatures Review

2021 ◽  
Author(s):  
Zhijun Liu ◽  
Ming-Feng You ◽  
Ya-Ling Wang ◽  
Yan Xu
Keyword(s):  
Genetic Testing ◽  
Ataxia Telangiectasia ◽  
Clinical Characteristics ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Chinese Family ◽  
Initial Symptom ◽  
Clinical Heterogeneity ◽  
The Family ◽  
Dominant Ataxia

Abstract Ataxia-telangiectasia (A-T) is an autosomal recessive disorder with high clinical heterogeneity. A-T may present in complicated variable forms, mainly including classic A-T and milder forms. Contrary to the classic A-T, the milder form does not present the cardinal features of A-T, including ataxia and telangiectasia. A few ATM mutations have been reported in variant A-T cases manifested as isolated dystonia without any signs of classical A-T. To date, more than 400 disease-related ATM mutations have been identified in patients with A-T. In this study, target exome-sequencing was performed in an AT pedigree with predominant dystonia. Two novel ATM mutations, p.I2683T and p.S2860P, were identified in the family. We then reviewed previously published literatures of genetically confirmed A-T cases with predominant dystonia and summarized the clinical characteristics of dystonia-dominant A-T. To our knowledge, this is the first report of A-T patient with predominant dystonia in China. Dystonia may appear as one of the predominant manifestations or initial symptom of A-T. ATM genetic testing should be early considered for those patients with predominant dystonia, despite without accompanying ataxia or telangiectasia.

scholarly journals Mitochondrial Neurogastrointestinal Encephalomyopathy Disease in Three Siblings from Pakistan with a Novel Mutation

2018 ◽  
Vol 08 (01) ◽  
pp. 015-019
Author(s):  
Sana Durrani ◽  
Bee Chen ◽  
Yusnita Yakob ◽  
Lua Hian ◽  
Bushra Afroze
Keyword(s):  
Thymidine Phosphorylase ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Gastrointestinal Symptoms ◽  
Autosomal Recessive Disorder ◽  
Homozygous Mutation ◽  
Pakistani Family ◽  
Mitochondrial Neurogastrointestinal Encephalomyopathy ◽  
Intestinal Dysmotility ◽  
Sensorineural Hearing Impairment

AbstractMitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare multisystem autosomal recessive disorder. The disease is clinically heterogeneous with gastrointestinal symptoms of intestinal dysmotility and cachexia as well as neurological symptoms of ophthalmoplegia, neuropathy, sensorineural hearing impairment, and diffuse leukoencephalopathy being most prominent. MNGIE is caused by mutations in TYMP, a gene that encodes thymidine phosphorylase (TP)—a cytosolic enzyme. Mutations in TYMP lead to very low TP catalytic activity, resulting in dramatically increased thymidine and deoxyuridine in plasma. We describe the clinical, biochemical, and neuroimaging findings of three boys with MNGIE from a Pakistani family with a novel homozygous mutation, c.798_801dupCGCG p. (Ala268Argfs*?), in exon 7 of TYMP.

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