Case Reports in Genetics最新文献_第6页

A Novel Pathogenic Variant in the RDH5 Gene in a Patient with Fundus Albipunctatus and Severe Macular Atrophy 白点眼底合并严重黄斑萎缩患者RDH5基因的一种新的致病变异

Case Reports in Genetics Pub Date : 2022-04-06 DOI: 10.1155/2022/1183772

H. You, David I Sierpina

{"title":"A Novel Pathogenic Variant in the RDH5 Gene in a Patient with Fundus Albipunctatus and Severe Macular Atrophy","authors":"H. You, David I Sierpina","doi":"10.1155/2022/1183772","DOIUrl":"https://doi.org/10.1155/2022/1183772","url":null,"abstract":"Purpose To report a novel 11-cis retinol dehydrogenase gene (RDH5) variant discovered in a 57-year-old male with fundus albipunctatus (FA) complicated by severe macular atrophy. Methods The patient was evaluated with a complete ophthalmic examination, optical coherence tomography (OCT), color fundus photography, green wavelength fundus autofluorescence, visual field testing, full-field ERG (ffERG), and multifocal ERG (mfERG). Genetic analysis investigating gene variants involved in inherited retinal disorders was performed. Results The patient presented with a rapid decline in visual acuity and a history of poor night vision. On fundoscopy, he exhibited a phenotype characteristic of FA accompanied by severe macular atrophy bilaterally. Heterozygous variants in the RDH5 gene were identified, including a novel missense variant, c.814_815del (p.Leu272Aspfs∗63), and a known pathogenic nonsense variant, c.160C > T (p.Arg54∗). Fundus autofluorescence demonstrated bull's eye maculopathy and hyperautofluorescent perifoveal rings bilaterally. OCT showed foveal atrophy of the outer retina and scattered hyper-reflective lesions in the peripheral macula. The ffERG results showed a severely diminished scotopic and photopic response. The mfERG results demonstrated minimal response in the central macula. Conclusions Fundus albipunctatus is a rare, congenital form of stationary night blindness caused almost exclusively by the RDH5 gene. This patient's clinical presentation, diagnostic studies, and genetic testing confirmed the diagnosis of FA. Additionally, he exhibited severe macular atrophy, not typically found in FA. Two RDH5 gene variants were identified, one of which is the novel variant, c.814_815del (p.Leu272Aspfs∗63). We suggest that this RDH5 genotype may be associated with a more progressive phenotype of FA contributing to macular atrophy.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85610988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism of Disease: Recessive ADAMTSL4 Mutations and Craniosynostosis with Ectopia Lentis 疾病机制:隐性ADAMTSL4突变与晶状体异位的颅缝闭闭

Case Reports in Genetics Pub Date : 2022-03-26 DOI: 10.1155/2022/3239260

Jonas A. Gustafson, Maria Bjork, C. V. van Ravenswaaij-Arts, M. Cunningham

{"title":"Mechanism of Disease: Recessive ADAMTSL4 Mutations and Craniosynostosis with Ectopia Lentis","authors":"Jonas A. Gustafson, Maria Bjork, C. V. van Ravenswaaij-Arts, M. Cunningham","doi":"10.1155/2022/3239260","DOIUrl":"https://doi.org/10.1155/2022/3239260","url":null,"abstract":"Craniosynostosis, the premature fusion of the calvarial bones, has numerous etiologies. Among them, several involve mutations in genes related to the TGFb signaling pathway, a critical molecular mediator of human development. These TGFb pathway-associated craniosynostosis syndromes include Loeys–Dietz syndrome (LDS) and Shprintzen–Goldberg syndrome (SGS). LDS and SGS have many similarities common to fibrillinopathies, specifically Marfan syndrome (MFS), which is caused by mutations in FBN1. Historically discriminating features of MFS from LDS and SGS are (1) the presence of ectopia lentis (the subluxation/dislocation of the ocular lens) and (2) the absence of craniosynostosis. Curiously, several instances of a seemingly novel syndrome involving only craniosynostosis and ectopia lentis have recently been reported to be caused by recessive mutations in ADAMTSL4, a poorly characterized gene as of yet. Here, we report on two new cases of craniosynostosis with ectopia lentis, each harboring recessive mutations in ADAMTSL4. We also discuss a proposed mechanism for the relationship between ADAMTSL4, FBN1, and TGFb pathway-related syndromes.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79319102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

The Efficacy of Anti-Tumor Necrosis Factor Therapy in Cryopyrin-Associated Periodic Syndromes: A Report of Two Cases 抗肿瘤坏死因子治疗冷冻素相关周期综合征2例疗效观察

Case Reports in Genetics Pub Date : 2022-03-03 DOI: 10.1155/2022/2898553

F. Tahghighi, Mahdieh Vahedi, N. Parvaneh, Mohammad Shahrooei, V. Ziaee

引用次数: 1

The Missing LNK: Evolution from Cytosis to Chronic Myelomonocytic Leukemia in a Patient with Multiple Sclerosis and Germline SH2B3 Mutation 缺失的LNK:多发性硬化症和种系SH2B3突变患者从细胞增生到慢性髓单细胞白血病的进化

Case Reports in Genetics Pub Date : 2022-03-01 DOI: 10.1155/2022/6977041

Krishna Gundabolu, B. Dave, C. Alvares, J. J. Cannatella, V. Bhatt, L. Maness, Z. Al-Kadhimi, R. Zabad, A. Cushman-Vokoun

{"title":"The Missing LNK: Evolution from Cytosis to Chronic Myelomonocytic Leukemia in a Patient with Multiple Sclerosis and Germline SH2B3 Mutation","authors":"Krishna Gundabolu, B. Dave, C. Alvares, J. J. Cannatella, V. Bhatt, L. Maness, Z. Al-Kadhimi, R. Zabad, A. Cushman-Vokoun","doi":"10.1155/2022/6977041","DOIUrl":"https://doi.org/10.1155/2022/6977041","url":null,"abstract":"Chronic myelomonocytic leukemia (CMML) is a rare but distinct hematological neoplasm with overlapping features of myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). Individuals with CMML have persistent monocytosis and bone marrow dyspoiesis associated with various constitutional symptoms like fevers, unintentional weight loss, or night sweats. It is established that there is a strong association of CMML with preceding or coexisting autoimmune diseases and systemic inflammatory syndromes affecting around 20% of patients. Various molecular abnormalities like TET2, SRSF2, ASXL1, and RAS are reported in the pathogenesis of CMML, but no such mutations have been described to explain the strong association of autoimmune diseases and severe inflammatory phenotype seen in CMML. Germline mutation in SH2B adaptor protein 3 (SH2B3) had been reported before to affect a family with autoimmune disorders and acute lymphoblastic leukemia. In this report, we describe the first case of a female subject with many years of preceding history of multiple sclerosis before the diagnosis of CMML. We outline the evidence supporting the pathogenic role of SH2B3 p.E395K germline mutation, connecting the dots of association between autoimmune diseases and CMML genesis.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82471148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Farber Disease Mimicking Juvenile Idiopathic Arthritis: The First Reported Case in Qatar and Review of the Literature. 法伯病模拟青少年特发性关节炎:卡塔尔首例报道病例及文献回顾。

Case Reports in Genetics Pub Date : 2022-02-10 eCollection Date: 2022-01-01 DOI: 10.1155/2022/2555235

Amal Al-Naimi, Haneen Toma, Sara G Hamad, Tawfeg Ben Omran

{"title":"Farber Disease Mimicking Juvenile Idiopathic Arthritis: The First Reported Case in Qatar and Review of the Literature.","authors":"Amal Al-Naimi, Haneen Toma, Sara G Hamad, Tawfeg Ben Omran","doi":"10.1155/2022/2555235","DOIUrl":"https://doi.org/10.1155/2022/2555235","url":null,"abstract":"Farber disease (FD) is an extremely rare autosomal recessive disorder caused by the deficiency of lysosomal acid ceramidase. It is characterized by a triad of progressive multiple joints' involvement, subcutaneous nodules, and hoarseness of voice. In this report, we describe a 23-month-old boy diagnosed with Farber disease. Initially, he was misdiagnosed as juvenile idiopathic arthritis (JIA) because he presented with joint swelling. However, the associated hoarseness of voice, subcutaneous nodules, and poor response to treatment all have questioned the diagnosis of JIA and prompted the suspicion of Farber disease as an alternative diagnosis. The diagnosis was later confirmed genetically by the presence of a homozygous pathogenic variant (p.Gly213Glu; c.638G > A in exon 8) in the ASAH1 gene. The present case illustrates the diagnostic journey of a child with Farber disease as well as highlights that FD should be considered in the differential diagnosis of early onset arthritis in the presence of subcutaneous nodules and/or hoarseness of voice.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":" ","pages":"2555235"},"PeriodicalIF":0.0,"publicationDate":"2022-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39940403","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: 4

The Benefits of Early versus Late Therapeutic Intervention in Fabry Disease. 法布里病早期与晚期治疗干预的益处

Case Reports in Genetics Pub Date : 2022-01-01 DOI: 10.1155/2022/3208810

Mónica Furlano, Elisabet Ars, Anna Matamala, Vicens Brossa, Joan Martí, Maria Del Prado-Venegas, Jaume Crespi, Esther Roe, Roser Torra

{"title":"The Benefits of Early versus Late Therapeutic Intervention in Fabry Disease.","authors":"Mónica Furlano, Elisabet Ars, Anna Matamala, Vicens Brossa, Joan Martí, Maria Del Prado-Venegas, Jaume Crespi, Esther Roe, Roser Torra","doi":"10.1155/2022/3208810","DOIUrl":"https://doi.org/10.1155/2022/3208810","url":null,"abstract":"Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants of the GLA gene. Heterozygous female patients may show much more variability in clinical manifestations, ranging from asymptomatic to full-blown disease. Because of this heterogeneous clinical picture in women, the diagnosis of FD has typically been delayed for more than a decade, and the optimal time to initiate treatment remains controversial. Case Presentation. Here, we present two unrelated female patients diagnosed with FD harbouring the same pathogenic GLA variant. We discuss the implications of initiating specific therapy at different stages of the disease, with and without organ involvement (early versus late therapeutic intervention).Conclusions: These clinical cases suggest that initiating specific treatment at an earlier age in women with FD may prevent organ involvement and associated clinical events.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2022 ","pages":"3208810"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9822754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10874717","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 Chinese Patient with Spastic Paraplegia Type 4 with a De Novo Mutation in the SPAST Gene. 中国4型痉挛性截瘫伴SPAST基因从头突变1例

Case Reports in Genetics Pub Date : 2021-12-14 eCollection Date: 2021-01-01 DOI: 10.1155/2021/6636855

Li Xu, Zijuan Peng, Chunhui Zhou, Jiqing Wang, Hunjin Luo, Qin Lu, Zhengjun Bao

{"title":"A Chinese Patient with Spastic Paraplegia Type 4 with a De Novo Mutation in the SPAST Gene.","authors":"Li Xu, Zijuan Peng, Chunhui Zhou, Jiqing Wang, Hunjin Luo, Qin Lu, Zhengjun Bao","doi":"10.1155/2021/6636855","DOIUrl":"https://doi.org/10.1155/2021/6636855","url":null,"abstract":"Background: Spastic paraplegia type 4 (SPG4) is the most common type of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. Case Presentation. We report the case of a 27-year-old pregnant Chinese woman with HSP in whom we identified a missense mutation in the SPAST gene (c.1496G>A, p.Arg499His) and a nonsense mutation in the NEFH gene (c.289G>T, p.Glu97 ∗ ) via whole-exome sequencing; this finding corroborated that of Sanger sequencing. The patient exhibited the pure SPG4 phenotype with onset during childhood. The SPAST mutation was absent in the parents and paternal relatives. However, the NEFH mutation was identified in five people with no clinical phenotype. Based on theoretical conjecture and the family gene segregation information, we concluded that the SPAST mutation, but not the NEFH mutation, accounted for the proband's phenotype. Eventually, the woman gave birth to a healthy baby girl with the NEFH mutation.Conclusion: In this report, we identified a missense mutation in the SPAST gene (p.Arg499His) in a 27-year-old pregnant Chinese woman with HSP. We believe that this study expands the knowledge about the clinical parameters and mutation spectrum of SPG4.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2021 ","pages":"6636855"},"PeriodicalIF":0.0,"publicationDate":"2021-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39759846","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

Delayed Diagnosis of McCune-Albright Syndrome. mcune - albright综合征的延迟诊断。

Case Reports in Genetics Pub Date : 2021-12-10 eCollection Date: 2021-01-01 DOI: 10.1155/2021/2999349

Bereket Fantahun, Seblewongel Desta

引用次数: 0

Whole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion. 全外显子组测序鉴定出一种新的POLG移码变异在成人患者进行性眼外肌麻痹和线粒体DNA缺失。

Case Reports in Genetics Pub Date : 2021-11-05 eCollection Date: 2021-01-01 DOI: 10.1155/2021/9969071

Justin Kurtz, Joseph Americo Fernandes, Mahesh Mansukhani, William C Copeland, Ali B Naini

{"title":"Whole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion.","authors":"Justin Kurtz, Joseph Americo Fernandes, Mahesh Mansukhani, William C Copeland, Ali B Naini","doi":"10.1155/2021/9969071","DOIUrl":"10.1155/2021/9969071","url":null,"abstract":"Mitochondrial DNA (mtDNA) depletion syndromes are a group of autosomal recessive disorders associated with a spectrum of clinical diseases, which include progressive external ophthalmoplegia (PEO). They are caused by variants in nuclear DNA (nDNA) encoded genes, and the gene that encodes for mtDNA polymerase gamma (POLG) is commonly involved. A splice-site mutation in POLG, c.3104+3A > T, was previously identified in three families with findings of PEO, and studies demonstrated this variant to result in skipping of exon 19. Here, we report a 57-year-old female who presented with ophthalmoplegia, ptosis, muscle weakness, and exercise intolerance with a subsequent muscle biopsy demonstrating mitochondrial myopathy on histopathologic evaluation and multiple mtDNA deletions by southern blot analysis. Whole-exome sequencing identified the previously characterized c. 3104+3A > T splice-site mutation in compound heterozygosity with a novel frameshift variant, p.Gly23Serfs ∗ 236 (c.67_88del). mtDNA copy number analysis performed on the patient's muscle showed mtDNA depletion, as expected in a patient with biallelic pathogenic mutations in POLG. This is the first reported case with POLG p.Gly23Serfs ∗ 236, discovered in a patient presenting with features of PEO.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2021 ","pages":"9969071"},"PeriodicalIF":0.0,"publicationDate":"2021-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39877299","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

Overlapping Phenotypes in Osteopetrosis and Pycnodysostosis in Asian-Indians. 亚洲-印度人骨质疏松症和骨质疏松症的重叠表型。

Case Reports in Genetics Pub Date : 2021-11-03 eCollection Date: 2021-01-01 DOI: 10.1155/2021/7133508

Parminder Kaur, Inusha Panigrahi, Harleen Kaur, Thakurvir Singh, Chakshu Chaudhry

引用次数: 2