Case Reports in Genetics最新文献

A De Novo Mutation in ACTC1 and a TTN Variant Linked to a Severe Sporadic Infant Dilated Cardiomyopathy Case.

Case Reports in Genetics Pub Date : 2024-12-28 eCollection Date: 2024-01-01 DOI: 10.1155/crig/9517735

Jose G Acuña-Ochoa, Norma A Balderrábano-Saucedo, Ana C Cepeda-Nieto, Maria Y Alvarado-Cervantes, Vianca L Ibarra-Garcia, Daniel Barr, Matthew J Gage, Ryan Pfeiffer, Dan Hu, Hector Barajas-Martinez

{"title":"A De Novo Mutation in ACTC1 and a TTN Variant Linked to a Severe Sporadic Infant Dilated Cardiomyopathy Case.","authors":"Jose G Acuña-Ochoa, Norma A Balderrábano-Saucedo, Ana C Cepeda-Nieto, Maria Y Alvarado-Cervantes, Vianca L Ibarra-Garcia, Daniel Barr, Matthew J Gage, Ryan Pfeiffer, Dan Hu, Hector Barajas-Martinez","doi":"10.1155/crig/9517735","DOIUrl":"https://doi.org/10.1155/crig/9517735","url":null,"abstract":"Structural or electrophysiologic cardiac anomalies may compromise cardiac function, leading to sudden cardiac death (SCD). Genetic screening of families with severe cardiomyopathies underlines the role of genetic variations in cardiac-specific genes. The present study details the clinical and genetic characterization of a malignant dilated cardiomyopathy (DCM) case in a 1-year-old Mexican child who presented a severe left ventricular dilation and dysfunction that led to SCD. A total of 132 genes (48 structure- and 84 electrical-related genes) were examined by next generation sequencing to identify potential causative mutations in comparison to control population. In silico analysis identified only two deleterious heterozygous mutations within an evolutionarily well-conserved region of the sarcomeric genes ACTC1/cardiac actin (c.664G > A/p.Ala222Thr) and TTN/titin (c.33250G > A/p.Glu11084Lys). Further pedigree analysis revealed the father of the index case to carry with the TTN mutation. Surprisingly, the ACTC1 mutation was not harbored by any first-degree family member. Computational 3D modeling of the mutated proteins showed electrostatic and conformational shifts of cardiac actin compared to wild-type version, as well as changes in the stability of the compact/folded states of titin that normally contributes to avoid mechanic damage. In conclusion, our findings suggest a likely pathogenic de novo mutation in ACTC1 in coexpression of a TTN variant as possible causes of an early onset of a severe DCM and premature death. These results may increase the known clinical pathogenic variations that may critically alter the structure of the heart, whose fatality could be prevented when rapidly detected.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2024 ","pages":"9517735"},"PeriodicalIF":0.0,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932665","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

Generalized Epileptic Seizures in Fibrodysplasia Ossificans Progressiva Harboring a Recurrent Heterozygous Variant of the ACVR1 Gene (R206H).

Case Reports in Genetics Pub Date : 2024-12-17 eCollection Date: 2024-01-01 DOI: 10.1155/crig/9569275

Kenichi Mishima, Hiroshi Kitoh, Anna Shiraki, Kenta Sawamura, Yasunari Kamiya, Masaki Matsushita, Shiro Imagama

{"title":"Generalized Epileptic Seizures in Fibrodysplasia Ossificans Progressiva Harboring a Recurrent Heterozygous Variant of the ACVR1 Gene (R206H).","authors":"Kenichi Mishima, Hiroshi Kitoh, Anna Shiraki, Kenta Sawamura, Yasunari Kamiya, Masaki Matsushita, Shiro Imagama","doi":"10.1155/crig/9569275","DOIUrl":"10.1155/crig/9569275","url":null,"abstract":"Background: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder caused by heterozygous ACVR1 pathogenic variants and is characterized by both progressive heterotopic ossification of the soft tissues and congenital malformations of the great toe. In addition to pathological skeletal metamorphosis, patients with FOP experience diverse neurological symptoms such as chronic pain and involuntary movements; however, little is known about the association between FOP and epileptic seizures. Methods: We report the case of a young boy with FOP who sustained multiple major fractures due to epileptic loss of consciousness. Results: Based on generalized electroencephalographic abnormalities and the presence of myoclonic movements, the patient was diagnosed with juvenile myoclonic epilepsy. The absence of seizures was well-controlled with valproic acid, whereas occasional abrupt myoclonic movements of the hands and feet persisted. Conclusion: This case expands our understanding of the phenotypic diversity of FOP and the functional versatility of ACVR1-mediated bone morphogenetic protein (BMP) signaling.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2024 ","pages":"9569275"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886260","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 Case Report on 13q12.3 Microdeletion Syndrome Caused by HMGB1 Haploinsufficiency.

Case Reports in Genetics Pub Date : 2024-11-27 eCollection Date: 2024-01-01 DOI: 10.1155/crig/1912620

Ting Wen, Brian J Shayota, Lauren Wallace, Coumarane Mani, Neal Davis, Jian Zhao

{"title":"A Case Report on 13q12.3 Microdeletion Syndrome Caused by HMGB1 Haploinsufficiency.","authors":"Ting Wen, Brian J Shayota, Lauren Wallace, Coumarane Mani, Neal Davis, Jian Zhao","doi":"10.1155/crig/1912620","DOIUrl":"10.1155/crig/1912620","url":null,"abstract":"Heterozygous microdeletions at 13q12.3 are associated with a rare genetic disorder, 13q12.3 microdeletion syndrome, characterized by intellectual disability, microcephaly, development delay, facial dysmorphisms, atopy, and obesity. Reported 13q12.3 microdeletions vary in size and typically encompass multiple genes. Previous studies have defined a minimal overlap region of 13q12.3 microdeletions and suggested that most of the phenotype associated with the 13q12.3 microdeletion syndrome could be attributed to the loss of the high mobility group box 1 (HMGB1) gene within the overlap region. Here, we report a pediatric patient who had typical phenotypic features of 13q12.3 microdeletion syndrome, including motor and moderate speech developmental delays, microcephaly, and severe atopy, along with anxiety and aggressive behaviors. Trio-based microarray analysis identified a 62-kb apparently de novo heterozygous deletion at 13q12.3 in the proband, fully encompassing all coding exons of the HMGB1 gene yet not affecting any other neighboring genes. This case report presents a rare HMGB1 single-gene deletion in a patient with classic features of 13q12.3 microdeletion syndrome, allowing a better delineation of clinical phenotypes associated with the loss of HMGB1. Our findings, together with previous reports, strongly support the pathogenic role of HMGB1 haploinsufficiency in the 13q12.3 microdeletion syndrome.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2024 ","pages":"1912620"},"PeriodicalIF":0.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781211","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

Geroderma Osteodysplastica With Concomitant Transposition of Great Vessels: A Case Report and Literature Review.

Case Reports in Genetics Pub Date : 2024-11-21 eCollection Date: 2024-01-01 DOI: 10.1155/crig/1397713

Charbel Saad, Christine Aoun, Charbel Iskandar, Tony Hayek, Maroun Matar, Andre Megarbane

{"title":"Geroderma Osteodysplastica With Concomitant Transposition of Great Vessels: A Case Report and Literature Review.","authors":"Charbel Saad, Christine Aoun, Charbel Iskandar, Tony Hayek, Maroun Matar, Andre Megarbane","doi":"10.1155/crig/1397713","DOIUrl":"https://doi.org/10.1155/crig/1397713","url":null,"abstract":"Geroderma Osteodysplastica (GO) is a rare autosomal recessive connective tissue disease characterized by wrinkled skin and osteoporosis, two distinct aging-related features. A loss of function mutation in GORAB results in the disease. Immediately after birth, a cyanotic female neonate was found to have transposition of great vessels (TGV) that was corrected with an uneventful surgical recovery. The patient was noted to have wrinkled skin and hyperlaxity in her joints. After a complete nutritional and metabolic panel, in addition to karyotyping, imaging, skin histopathology analysis, and genetic testing she was found to have GO. We found two novel compound heterozygous mutations in GORAB: p.Asp236∗ and pAsp236Ala. This is the first study that reports the concurrent incidence of GO with TGV. The patient was started on bisphosphonates, which led to a reduction in the occurrence of fractures. An early diagnosis of GO is warranted to prevent or reduce bone density loss due to osteoporosis via initiation of bisphosphonate treatment. Whole exome sequencing remains the gold standard for diagnosing GO and ruling out phenotypically similar disorders.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2024 ","pages":"1397713"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772566","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

Intellectual Disability and Blended Phenotypes: Insights from a Centre in North India. 智力残疾与混合表型：来自印度北部一个中心的启示。

Case Reports in Genetics Pub Date : 2024-08-22 eCollection Date: 2024-01-01 DOI: 10.1155/2024/6009569

Inusha Panigrahi, Sudha Rao, Shalu Verma Kumar, Divya Kumari, Parminder Kaur

引用次数: 0

A De Novo Missense MYLK Variant Leading to Nonsyndromic Thoracic Aortic Aneurysm and Dissection Identified by Segregation Analysis. 通过分离分析发现的导致非综合征性胸主动脉瘤和夹层的新缺失MYLK变异体

Case Reports in Genetics Pub Date : 2024-08-16 eCollection Date: 2024-01-01 DOI: 10.1155/2024/4281972

Daigo Nishijo, Hiroki Yagi, Nana Akiyama, Norifumi Takeda, Masahiko Ando, Haruo Yamauchi, Norihiko Takeda, Issei Komuro

{"title":"A De Novo Missense MYLK Variant Leading to Nonsyndromic Thoracic Aortic Aneurysm and Dissection Identified by Segregation Analysis.","authors":"Daigo Nishijo, Hiroki Yagi, Nana Akiyama, Norifumi Takeda, Masahiko Ando, Haruo Yamauchi, Norihiko Takeda, Issei Komuro","doi":"10.1155/2024/4281972","DOIUrl":"10.1155/2024/4281972","url":null,"abstract":"Nonsyndromic hereditary thoracic aortic aneurysm and dissection (TAAD) is an autosomal dominant disease; however, it is frequently difficult to identify the causative genes. We report in this study a 33-year-old Japanese male with TAAD (Stanford type A) that is complicated with severe aortic regurgitation. There was no family history of aortic diseases in the patient nor any specific clinical features suggestive of connective tissue diseases, such as Marfan syndrome. Genetic testing identified candidate causative variants in two different genes: MYLK (c.4819G > A, p.[Gly1607Ser]) and FBN1 (c.365G > A, p.[Arg122His]). Familial cosegregation analysis revealed that the novel de novo MYLK variant was present only in the proband, and the FBN1 variant was also found in his nonaffected mother, and thus the MYLK variant was classified as likely pathogenic. MYLK is a causative gene for nonsyndromic TAAD that requires careful management; however, the number of reports is limited. Accumulating data on the pathogenicity of rare variants by performing a comprehensive pedigree analysis would help establish better treatment strategies for life-threatening hereditary TAAD cases.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2024 ","pages":"4281972"},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056713","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

Two Pediatric Cases of Primary Ciliary Dyskinesia Caused by Loss-of-Function Variants in Oral-Facial-Digital Syndrome Gene, OFD1. 由口腔-面部-数字综合征基因 OFD1 功能缺失变异引起的两例小儿原发性睫状肌运动障碍。

Case Reports in Genetics Pub Date : 2024-08-09 eCollection Date: 2024-01-01 DOI: 10.1155/2024/1595717

Yifei Xu, Yuki Tsurinaga, Tsubasa Matsumoto, Ryuji Muta, Taichi Yano, Hiroshi Sakaida, Sawako Masuda, Koki Ueda, Guofei Feng, Shimpei Gotoh, Satoru Ogawa, Makoto Ikejiri, Kaname Nakatani, Mizuho Nagao, Masaki Tanabe, Kazuhiko Takeuchi

引用次数: 0

Discovery of a Novel DYRK1A Mutation (c.524del) in Intellectual Development Disorder Autosomal Dominant 7 (MRD7): A Comprehensive Case Analysis. 在智力发育障碍常染色体显性遗传 7 (MRD7) 中发现新型 DYRK1A 突变（c.524del）：综合病例分析。

Case Reports in Genetics Pub Date : 2024-07-30 eCollection Date: 2024-01-01 DOI: 10.1155/2024/2926555

Fiona Whitaker, Alvaro Serrano

引用次数: 0

Phenotype-Genotype Discordance and a Case of a Disorder of Sexual Differentiation. 表型-基因型不一致和一个性分化障碍病例。

Case Reports in Genetics Pub Date : 2024-07-17 eCollection Date: 2024-01-01 DOI: 10.1155/2024/9936936

Madeline Snipes, Stephanie Stokes, Amy Vidalin, Lee D Moore, Natalia Schlabritz-Lutsevich, James Maher

引用次数: 0

A Fatal Case of 3-Hydroxyisobutyryl-CoA Hydrolase Deficiency in a Term Infant with Severe High Anion Gap Acidosis and Review of the Literature. 一个患有 3-羟基异丁酰-CoA水解酶缺乏症并伴有严重高阴离子差酸中毒的足月婴儿死亡病例及文献综述。

Case Reports in Genetics Pub Date : 2024-06-30 eCollection Date: 2024-01-01 DOI: 10.1155/2024/8099373

Surasak Puvabanditsin, Ian Lee, Natasha Cordero, Keisha Target, Su Young Park, Rajeev Mehta

引用次数: 0