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.

Case Report: A New Spectroscopy Finding in Infantile Neuroaxonal Dystrophy

2018 ◽  
Vol 17 (05) ◽  
pp. 180-183
Author(s):  
Andrew Martin ◽  
Saharwash Jamali ◽  
Natasha Redhead ◽  
Paul Armitage ◽  
Archana Desurkar ◽  
...  
Keyword(s):  
Case Report ◽  
Genetic Testing ◽  
Basal Ganglia ◽  
Female Patient ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Cerebellar Vermis ◽  
Neuroaxonal Dystrophy ◽  
Infantile Neuroaxonal Dystrophy ◽  
Motor Delay

AbstractInfantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive disorder that is associated with developmental delay and regression. A female patient of consanguineous parents presented with gross motor delay at 15 months. She was known to have two paternal uncles who had died with a diagnosis of INAD. Over the next 15 months, she exhibited regression in several domains and following genetic testing was diagnosed with a PLA2G6 mutation in keeping with INAD. The cerebellar vermis demonstrated a significant reduction in the N-acetylaspartate/creatinine (NAA/Cr) ratio of 0.69. This case highlights what we believe to be a new imaging feature of a low NAA/Cr ratio in the cerebellar vermis with normal ratios in the cerebellar hemispheres and basal ganglia in a patient with genetically confirmed diagnosis of INAD.

scholarly journals The Natural History of Infantile Neuroaxonal Dystrophy

2020 ◽  
Author(s):  
Fadie D Altuame ◽  
Gretchen Foskett ◽  
Paldeep Atwal ◽  
Sarah Endemann ◽  
Mark Midei ◽  
...  
Keyword(s):  
Natural History ◽  
Neurodegenerative Disorder ◽  
Gastrointestinal Disease ◽  
Cerebellar Atrophy ◽  
Neuroaxonal Dystrophy ◽  
Fine Motor ◽  
Speech Impairment ◽  
Infantile Neuroaxonal Dystrophy ◽  
Significant Difference ◽  
History Of

Abstract Background: Infantile neuroaxonal dystrophy (INAD) is a rapidly progressive neurodegenerative disorder of early onset causing premature death. It results from biallelic pathogenic variants in PLA2G6, which encodes a calcium‐independent phospholipase A2. Objective: We aim to outline the natural history of INAD and provide a comprehensive description of its clinical, radiological, laboratory, and molecular findings. Materials and Methods: We comprehensively analyzed the charts of 28 patients: 16 patients from Riyadh, Saudi Arabia, 8 patients from North and South America and 4 patients from Europe with a molecularly confirmed diagnosis of PLA2G6‐associated neurodegeneration (PLAN) and a clinical history consistent with INAD.Results: In our cohort, speech impairment and loss of gross motor milestones were the earliest signs of the disease. As the disease progressed, loss of fine motor milestones and bulbar dysfunction were observed. Temporo-frontal function was among the last of the milestones to be lost. Appendicular spastic hypertonia, axial hypotonia, and hyperreflexia were common neurological findings. Other common clinical findings include nystagmus (60.7%), seizures (42.9%), gastrointestinal disease (42.9%), skeletal deformities (35.7%), and strabismus (28.6%). Cerebellar atrophy and elevations in serum AST and LDH levels were consistent features of INAD. There was a statistically significant difference when comparing patients with non-sense/truncating variants compared with missense/in-frame deletions in the time of initial concern (p = 0.04), initial loss of language (p = 0.001), initial loss of fine motor skills (p = 0.009), and initial loss of bulbar skills (p = 0.007).Conclusion: INAD is an ultra-rare neurodegenerative disorder that presents in early childhood, with a relentlessly progressive clinical course. Knowledge of the natural history of INAD may serve as a resource for healthcare providers to develop a targeted care plan and may facilitate the design of clinical trials to treat this disease.

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.

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.

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.

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 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.

scholarly journals The Natural History of Infantile Neuroaxonal Dystrophy

2020 ◽  
Author(s):  
Fadie D Altuame ◽  
Gretchen Foskett ◽  
Paldeep Atwal ◽  
Sarah Endemann ◽  
Mark Midei ◽  
...  
Keyword(s):  
Natural History ◽  
Neurodegenerative Disorder ◽  
Gastrointestinal Disease ◽  
Cerebellar Atrophy ◽  
Neuroaxonal Dystrophy ◽  
Fine Motor ◽  
Speech Impairment ◽  
Infantile Neuroaxonal Dystrophy ◽  
Significant Difference ◽  
History Of

Abstract Background Infantile neuroaxonal dystrophy (INAD) is a rapidly progressive neurodegenerative disorder of early onset causing premature death. It results from biallelic pathogenic variants in PLA2G6 , which encodes a calcium‐independent phospholipase A2. Objective We aim to outline the natural history of INAD and provide a comprehensive description of its clinical, radiological, laboratory, and molecular findings. Materials and Methods We comprehensively analyzed the charts of 28 patients: 16 patients from Riyadh, Saudi Arabia, 8 patients from North and South America and 4 patients from Europe with a molecularly confirmed diagnosis of PLA2G6 ‐associated neurodegeneration (PLAN) and a clinical history consistent with INAD. Results In our cohort, speech impairment and loss of gross motor milestones were the earliest signs of the disease. As the disease progressed, loss of fine motor milestones and bulbar dysfunction were observed. Temporo-frontal function was among the last of the milestones to be lost. Appendicular spastic hypertonia, axial hypotonia, and hyperreflexia were common neurological findings. Other common clinical findings include nystagmus (60.7%), seizures (42.9%), gastrointestinal disease (42.9%), skeletal deformities (35.7%), and strabismus (28.6%). Cerebellar atrophy and elevations in serum AST and LDH levels were consistent features of INAD. There was a statistically significant difference when comparing patients with non-sense/truncating variants compared with missense/in-frame deletions in the time of initial concern (p = 0.04), initial loss of language (p = 0.001), initial loss of fine motor skills (p = 0.009), and initial loss of bulbar skills (p = 0.007). Conclusion INAD is an ultra-rare neurodegenerative disorder that presents in early childhood, with a relentlessly progressive clinical course. Knowledge of the natural history of INAD may serve as a resource for healthcare providers to develop a targeted care plan and may facilitate the design of clinical trials to treat this disease.

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