Case Reports in Genetics最新文献_第7页

Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia. 斯里兰卡特发性共济失调患者的六种新型 ATM 基因变异。

Case Reports in Genetics Pub Date : 2020-12-09 eCollection Date: 2020-01-01 DOI: 10.1155/2020/6630300

D Hettiarachchi, Hetalkumar Panchal, B A P S Pathirana, P D Rathnayaka, A Padeniya, P S Lai, V H W Dissanayake

{"title":"Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia.","authors":"D Hettiarachchi, Hetalkumar Panchal, B A P S Pathirana, P D Rathnayaka, A Padeniya, P S Lai, V H W Dissanayake","doi":"10.1155/2020/6630300","DOIUrl":"10.1155/2020/6630300","url":null,"abstract":"Introduction: Ataxia telangiectasia is a rare genetic condition with an estimated prevalence of 1 in 40,000-100,000 live births. This condition predominantly affects the nervous and immune systems. It is characterized by progressive ataxia beginning from early childhood. The neurological deficit associated with this condition affects one's balance, coordination, walking, and speech and can be accompanied by chorea, myoclonus, and neuropathy. They may also have ocular telangiectasias and high levels of blood alpha-fetoprotein (AFP). The ataxia telangiectasia mutated gene (ATM) is associated with this condition and codes for the ATM protein which is a phosphatidylinositol 3-kinase. This gene occupies 150 kb on chromosome 11q22-23 and contains 66 exons encoding a 13 kb transcript. ATM is a relatively large protein with a molecular weight of 350 kDa and 3,056 amino acids.Methods: Four patients of Sri Lankan origin presenting with features suggestive of ataxia telangiectasia were referred to our genetics center for specialized genetic counseling and testing. Whole-exome sequencing followed by Sanger sequencing was used to confirm the candidate variants. Protein modeling and genotype to phenotype correlation was performed in the identified variants.Results: We observed 6 novel ATM gene variants in four patients with ataxia telangiectasia. The identified variants are as follows: homozygous c.7397C > A (p.Ala2466Glu) and c.510_511delGT (p.Tyr171fs) and compound heterozygous c.5347_5350delGAAA (p.Glu1783fs), c.8137A > T (p.Arg2713 ∗ ) and c.1163A > C (p.Lys388Thr), and c.5227A > C (p.Thr1743Pro). Variant analysis was followed by modeling of the native and altered protein structures.Conclusion: We report novel ATM gene variants that have implications on the molecular diagnosis of ataxia telangiectasia.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39110636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Specific Diplotype H1j/H2 of the MAPT Gene Could Be Responsible for Parkinson's Disease with Dementia. MAPT基因的一种特殊双倍型H1j/H2可能是帕金森病伴痴呆的原因。

Case Reports in Genetics Pub Date : 2020-12-03 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8813344

Imane Smaili, Imane Hajjaj, Rachid Razine, Houyam Tibar, Ayyoub Salmi, Naima Bouslam, Ahmed Moussa, Wafa Regragui, Ahmed Bouhouche

{"title":"A Specific Diplotype H1j/H2 of the MAPT Gene Could Be Responsible for Parkinson's Disease with Dementia.","authors":"Imane Smaili, Imane Hajjaj, Rachid Razine, Houyam Tibar, Ayyoub Salmi, Naima Bouslam, Ahmed Moussa, Wafa Regragui, Ahmed Bouhouche","doi":"10.1155/2020/8813344","DOIUrl":"https://doi.org/10.1155/2020/8813344","url":null,"abstract":"Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. Five to ten percent of patients have monogenic form of the disease, while most of sporadic PD cases are caused by the combination of genetic and environmental factors. Microtubule-associated protein tau (MAPT) has been appointed as one of the most important risk factors for several neurodegenerative diseases including PD. MAPT is characterized by an inversion in chromosome 17 resulting in two distinct haplotypes H1 and H2. Studies described a significant association of MAPT H1j subhaplotype with PD risk, while H2 haplotype was associated with Parkinsonism, particularly to its bradykinetic component. We report here an isolated case displaying an akinetic-rigid form of PD, with age of onset of 41 years and a good response to levodopa, who developed dementia gradually during the seven years of disease progression. The patient does not carry the LRRK2 G2019S mutation, copy number variations, nor pathogenic and rare variants in known genes associated with PD. MAPT subhaplotype genotyping revealed that the patient has the H1j/H2 diplotype, his mother H1j/H1j, his two healthy brothers H1j/H1v and his deceased father was by deduction H1v/H2. The H1j/H2 diplotype was shown in a total of 3 PD patients among 80, who also did not have known PD-causing mutation and in 1 out of 92 healthy individual controls. The three patients with this diplotype all have a similar clinical phenotype. Our results suggest that haplotypes H1j and H2 are strong risk factor alleles, and their combination could be responsible for early onset of PD with dementia.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38733501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Multimodal Imaging Characteristics of ADRP in a Family with p.Thr58Arg Substituted RHO Mutation. p.Thr58Arg取代RHO突变家族ADRP的多模态成像特征

Case Reports in Genetics Pub Date : 2020-12-02 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8860863

Misty Ruppert, John Pyun, K V Chalam, David Sierpina

{"title":"Multimodal Imaging Characteristics of ADRP in a Family with p.Thr58Arg Substituted RHO Mutation.","authors":"Misty Ruppert, John Pyun, K V Chalam, David Sierpina","doi":"10.1155/2020/8860863","DOIUrl":"https://doi.org/10.1155/2020/8860863","url":null,"abstract":"Background: Autosomal dominant retinitis pigmentosa (adRP) is a rare cause of progressive visual impairment in young patients and is frequently a result of RHO gene mutations. p.Thr58Arg rhodopsin mutation leads to misfolding of rhodopsin, subsequent accumulation in the endoplasmic reticulum, and leads to consecutive atrophy of photoreceptor cells through apoptosis.Materials and methods: We describe multimodal imaging findings in a 58-year-old female with adRP due to a c.173 C > G, p.Thr58Arg rhodopsin mutation (confirmed on genotyping), including ultra-wide-field fundus autofluorescence (UWF-FAF), color scanning laser ophthalmoscopy, structural optical coherence tomography (OCT), OCT-angiography (OCT-A), electroretinography (ERG), and visual field testing (HVF). Additionally, we compare the patient's phenotypic findings to those of her offspring, who was also affected by adRP.Results: The 58-year-old female and her son with symptoms of nyctalopia and decreased vision showed macular pigmentary changes in a bull's-eye pattern along with bone spicules in periphery with retinal atrophy. Genotyping confirmed p.Thr58Arg rhodopsin mutation. Wide area of dystrophic retina was noted on UWF-FAF, along with corresponding atrophy of photoreceptor layer on OCT. OCTA revealed complete nonperfusion of the superficial capillary plexus in areas of retinal dystrophy. ERG revealed increased latency and decreased amplitudes; HVF revealed constriction of visual fields consistent with retinal findings.Conclusions: Multimodal imaging is extremely helpful in delineating the extent of retinal dystrophy and comparable to ERG for monitoring of progress in retinitis pigmentosa. Photoreceptor layer thickness (measured with OCT) strongly correlated with ERG and can be used as a secondary surrogate for monitoring the disease progress.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25525090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cytogenomic Abnormalities in 19 Cases of Salivary Gland Tumors of Parotid Gland Origin. 腮腺源性唾液腺肿瘤19例细胞基因组异常分析。

Case Reports in Genetics Pub Date : 2020-12-02 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8897541

Marie Zerjav, Autumn DiAdamo, Brittany Grommisch, Amato Katherine, Hongyan Chai, Gang Peng, Peining Li

引用次数: 1

Genetic Testing Distinguishes Multiple Chondroid Chordomas with Neuraxial Bone Metastases from Multicentric Tumors. 基因检测区分多发性软骨样脊索瘤伴轴向骨转移与多中心肿瘤。

Case Reports in Genetics Pub Date : 2020-11-28 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8877722

Hiroshi Kobayashi, Masahiro Shin, Naohiro Makise, Aya Shinozaki-Ushiku, Masachika Ikegami, Yuki Taniguchi, Yusuke Shinoda, Shinji Kohsaka, Tetsuo Ushiku, Katsutoshi Oda, Kiyoshi Miyagawa, Hiroyuki Aburatani, Hiroyuki Mano, Sakae Tanaka

{"title":"Genetic Testing Distinguishes Multiple Chondroid Chordomas with Neuraxial Bone Metastases from Multicentric Tumors.","authors":"Hiroshi Kobayashi, Masahiro Shin, Naohiro Makise, Aya Shinozaki-Ushiku, Masachika Ikegami, Yuki Taniguchi, Yusuke Shinoda, Shinji Kohsaka, Tetsuo Ushiku, Katsutoshi Oda, Kiyoshi Miyagawa, Hiroyuki Aburatani, Hiroyuki Mano, Sakae Tanaka","doi":"10.1155/2020/8877722","DOIUrl":"https://doi.org/10.1155/2020/8877722","url":null,"abstract":"Background: Chordomas are rare malignant bone tumors preferentially forming in neuraxial bones. Chondroid chordoma is a subtype of chordoma. Chordomas reportedly present as synchronous multiple lesions upon initial diagnosis. However, it remains unknown whether these lesions are multicentric or metastatic multiple chordoma tumors. Case Presentation. Here, we present the case of a 57-year-old woman with multiple chordomas at the clivus, C6, and T12 upon initial presentation. Sequential surgeries and radiotherapy were performed for these lesions, and postoperative histological diagnosis revealed that all lesions were chondroid chordomas. Next-generation sequencing revealed that these lesions harbored a common somatic mutation in epidermal growth factor receptor (EGFR), c.3617A>C, which is not considered a pathogenic chordoma mutation, thus indicating that these lesions were not multicentric but rather multiple metastatic tumors. Subsequent multiple metastases to the lung and appendicular and axial bones were detected 15 months after the initial surgery. Recurrent lesions at the clivus progressed despite EGFR-targeted therapy, surgery, and radiotherapy.Conclusion: The present evidence indicates that multiple chordomas in this case were caused by multiple metastases rather than multicentric lesions. Multiple presentations of chordoma imply systemic dissemination of tumor cells, and novel efficient systemic therapy is required to treat this disease.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8877722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38707004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Corrigendum to "Eye Manifestations of Shprintzen-Goldberg Craniosynostosis Syndrome: A Case Report and Systematic Review". Shprintzen-Goldberg 颅骨发育不良综合征的眼部表现：病例报告和系统回顾 "的更正。

Case Reports in Genetics Pub Date : 2020-11-11 eCollection Date: 2020-01-01 DOI: 10.1155/2020/4708976

Jamie H Choi, Rachel Li, Rachel Gannaway, Tahnee N Causey, Anna Harrison, Natario L Couser

引用次数: 0

Hyperkalemic Periodic Paralysis: Case Report with a SCNA4 Gene Mutation and Literature Review. 高钾血症性周期性麻痹:SCNA4基因突变1例报告及文献复习。

Case Reports in Genetics Pub Date : 2020-10-16 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8843410

Manuela Quiroga-Carrillo, Cristian Correa-Arrieta, Fernando Ortiz-Corredor, Fernando Suarez-Obando

引用次数: 1

Acute Intermittent Porphyria in a Man with Dual Enzyme Deficiencies. 双酶缺乏症患者急性间歇性卟啉症。

Case Reports in Genetics Pub Date : 2020-10-15 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8873219

G N Cerbino, L Abou Assali, L S Varela, L Tomassi, A Batlle, V E Parera, M V Rossetti

引用次数: 1

Very-Long-Chain Acyl-Co-Enzyme A Dehydrogenase Deficiency Presenting as Rhabdomyolysis: First Case Report from Sri Lanka. 以横纹肌溶解为表现的超长链酰基辅酶A脱氢酶缺乏:斯里兰卡首例报告。

Case Reports in Genetics Pub Date : 2020-10-13 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8894518

Maheshi Wijayabandara, Champika Gamakaranage, Dineshani Hettiarachchi

{"title":"Very-Long-Chain Acyl-Co-Enzyme A Dehydrogenase Deficiency Presenting as Rhabdomyolysis: First Case Report from Sri Lanka.","authors":"Maheshi Wijayabandara, Champika Gamakaranage, Dineshani Hettiarachchi","doi":"10.1155/2020/8894518","DOIUrl":"https://doi.org/10.1155/2020/8894518","url":null,"abstract":"Background: Rhabdomyolysis can be either inherited or acquired such as in metabolic myopathies. Very-long-chain acyl-CoA dehydrogenase deficiency is a rare fatty acid oxidation disorder which presents with different phenotypes, and the mild adult form can present as intermittent rhabdomyolysis. Here, we present the first adult case of very-long-chain acyl-CoA dehydrogenase deficiency presenting as rhabdomyolysis in a Sri Lankan patient. Case Presentation. A 36-year-old Sri Lankan man who was born to consanguineous parents presented with severe generalized muscle pain, stiffness, and dark-coloured urine for three days following prolonged low-intensity activity. Since fourteen years of age, he has had multiple similar episodes, where one episode was complicated with acute kidney injury. His eldest brother also suffered from the similar episode. Examination revealed only generalized muscle tenderness without any weakness. His creatine phosphokinase level was above 50,000 IU/L, and he had myoglobinuria. Molecular genetic tests confirmed the diagnosis of very-long-chain acyl-CoA dehydrogenase deficiency. Following a successful recovery devoid of complications, he remained asymptomatic with lifestyle adjustments.Conclusion: Very-long-chain acyl-CoA dehydrogenase deficiency is a rare inherited cause of metabolic myopathy that gives rise to intermittent rhabdomyolysis in adults. Prompt diagnosis is essential to prevent complications and prevent its recurrence.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8894518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38533837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Hepatocellular Carcinoma in a 24-Year-Old Female with Beckwith-Wiedemann Syndrome: A Case Report and Review of the Literature. 一名 24 岁女性贝克维特-维德曼综合征患者的肝细胞癌：病例报告与文献综述。

Case Reports in Genetics Pub Date : 2020-10-07 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8811296

Carolyn G Ahlers, Quoc-Huy Trinh, Martin Montenovo

引用次数: 0