Clinical Genetics最新文献_第6页

Identification of a Novel FLT4 c.3028A>C Variant Associated With Milroy Disease. 一种与Milroy病相关的FLT4 C . 3028a >C新变异的鉴定

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-12-18 DOI: 10.1111/cge.14671

Aygiz Feiskhanov, Aigul Ibragimova, Elina Gaysina, Eugenia Boulygina, Albert Rizvanov, Regina Miftakhova, Yulia Filina

引用次数: 0

A Variable Clinical Presentation of Hemoglobin City of Hope. 血红蛋白希望之城的临床表现变化。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-12-18 DOI: 10.1111/cge.14675

Dafna Brik Simon, Dvora Filon, Vardiella Meiner, Tanya Krasnov, Sharon Noy-Lotan, Orly Dgany, Oded Gilad, Tracie Goldberg, Shai Izraeli, Joanne Yacobovich, Hannah Tamary, Orna Steinberg-Shemer

{"title":"A Variable Clinical Presentation of Hemoglobin City of Hope.","authors":"Dafna Brik Simon, Dvora Filon, Vardiella Meiner, Tanya Krasnov, Sharon Noy-Lotan, Orly Dgany, Oded Gilad, Tracie Goldberg, Shai Izraeli, Joanne Yacobovich, Hannah Tamary, Orna Steinberg-Shemer","doi":"10.1111/cge.14675","DOIUrl":"https://doi.org/10.1111/cge.14675","url":null,"abstract":"Hemoglobin City of Hope (Hb-COH), NC_000011.9(NM_000518.5):c.208G > A; NP_000509.1:p.(Gly70Ser), has rarely been described. The presentation ranges from asymptomatic heterozygosity to significant anemia in patients carrying an additional pathogenic variant in β-globin. To elucidate the clinical spectrum of Hb-COH, we analyzed 31 individuals carrying the variant, including, for the first time, homozygous individuals. Seven patients who were compound heterozygous for Hb-COH and an additional variant in β-globin, presented with mild-to-severe microcytic anemia and elevated hemoglobin-A2. Three (43%) of these also had elevated fetal hemoglobin, but none required blood transfusions. Seven patients coinherited Hb-COH with an -α3.7-deletion (NG_000006.1:g.34247_38050del), their presentation ranged from mild microcytic anemia to normal blood counts. Three homozygous and 14 heterozygous individuals for Hb-COH had normal blood counts. Most Hb-COH alleles whose origin was traceable were from Ashkenazi Jews (70.4%). To conclude, while isolated Hb-COH appears asymptomatic even in the homozygous state, it may cause significant anemia when coinherited with an additional pathogenic variant in β-globin. Understanding the full impact of Hb-COH is crucial for optimal patient management and for genetic counseling.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Homozygous ASTN1 Nonsense Variant Linked to Epileptic Encephalopathy: A Detailed Report With Unique Clinical Presentation. 纯合子ASTN1无义变异与癫痫性脑病相关：具有独特临床表现的详细报告。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-12-12 DOI: 10.1111/cge.14674

Akif Ayaz, Safiye Güneş Sager, Ahmet Sercan Gökşen, Kıvanç Kök, Emine Caliskan, Omar Alomari

引用次数: 0

Clinical and Genetic Analysis of Digenic Muscular Dystrophy due to SRPK3 and TTN Variants in Two Siblings. 兄弟姐妹中SRPK3和TTN变异引起的遗传性肌营养不良的临床和遗传分析。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-12-12 DOI: 10.1111/cge.14673

Inna Sharkova, Artem Borovikov, Fedor Konovalov, Maria Nefedova, Olga Shchagina, Sergey Kutsev, Aysylu Murtazina

{"title":"Clinical and Genetic Analysis of Digenic Muscular Dystrophy due to SRPK3 and TTN Variants in Two Siblings.","authors":"Inna Sharkova, Artem Borovikov, Fedor Konovalov, Maria Nefedova, Olga Shchagina, Sergey Kutsev, Aysylu Murtazina","doi":"10.1111/cge.14673","DOIUrl":"https://doi.org/10.1111/cge.14673","url":null,"abstract":"We present a family with two male siblings diagnosed with a newly described digenic myopathy, involving likely pathogenic loss-of-function variants in the SRPK3 and TTN genes: hemizygous p.(Pro68ArgfsTer55) and heterozygous p.(Trp14174Ter), respectively. Both siblings experienced prenatal disease onset, characterized by weak fetal movements, but showed significant clinical improvement over two last years of our follow-up. Key features included early onset, delayed motor development, and prominent axial and proximal weakness, while adult variants' carriers remained asymptomatic, without any myopathic or cardiac manifestations. Lower limb MRI revealed distinctive abnormalities, with different patterns between the siblings: the older brother showed more pronounced involvement of the thigh muscles, while the younger brother exhibited greater changes in the lower leg muscles. Given the early stage of the disease in our patients and the initial changes observed on MRI, we suggest that the semitendinosus and vastus lateralis muscles are primarily involved at the thigh level in SRPK3/TTN-myopathy. This case highlights the importance of considering digenic inheritance in neuromuscular disorders and underscores the necessity of comprehensive genetic analysis in similar cases.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Concomitant Upd(14)mat and Trisomy 14 Mosaicism in a Newborn Detected by Whole Genome Sequencing. 新生儿Upd(14)mat和14三体嵌合现象的全基因组测序

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-12-12 DOI: 10.1111/cge.14676

Tilde Olsen, Jakob Ek, Mads Bak, Karen Grønskov, Iben Bache, Stense Farholt, Zeynep Tümer

引用次数: 0

Diagnostic Use of Genome Sequencing in Patients With 11p15.5 Imprinting Disorder Features: A Pilot Study. 基因组测序在11p15.5印迹障碍特征患者中的诊断应用：一项初步研究

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-12-12 DOI: 10.1111/cge.14649

Luise Kessler, Jeremias Krause, Florian Kraft, Asmaa K Amin, Gyorgy Fekete, Anna Lengyel, Eva Pinti, Arpad Kovacs, Annette Lischka, Katja Eggermann, Ingo Kurth, Cordula Knopp, Miriam Elbracht, Matthias Begemann, Thomas Eggermann

{"title":"Diagnostic Use of Genome Sequencing in Patients With 11p15.5 Imprinting Disorder Features: A Pilot Study.","authors":"Luise Kessler, Jeremias Krause, Florian Kraft, Asmaa K Amin, Gyorgy Fekete, Anna Lengyel, Eva Pinti, Arpad Kovacs, Annette Lischka, Katja Eggermann, Ingo Kurth, Cordula Knopp, Miriam Elbracht, Matthias Begemann, Thomas Eggermann","doi":"10.1111/cge.14649","DOIUrl":"https://doi.org/10.1111/cge.14649","url":null,"abstract":"To assess the suitability of genome sequencing (GS) as the second step in the diagnostics of patients with the features of 11p15.5-associated imprinting disorders (ImpDis: Silver-Russell syndrome [SRS], Beckwith-Wiedemann syndrome [BWS]), we performed short-read GS in patients negatively tested for imprinting disturbances. Obtaining a genetic diagnosis for patients with the features of these syndromes is challenging due to the clinical and molecular heterogeneity and overlap, and many patients remain undiagnosed after the currently suggested stepwise diagnostic workup. GS was conducted in 48 patients (SRS features: n = 37 and BWS features: n = 11). The detection rate differed markedly between the ImpDis: although a genetic cause could be identified in 51% of patients referred with SRS features, no pathogenic variants were detected in patients with BWS features. Thus, GS substantially improves the diagnostic yield and broadens the spectrum of overlapping disorders with SRS features. Obtaining a precise molecular diagnosis provides the basis for a personalized clinical management. Our findings support the use of GS as a second-tier diagnostic tool for patients with growth disturbances, as it addresses all currently known variant types and shortens the diagnostic odyssey.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mismatch Repair Proficient Colorectal Adenocarcinoma in Two Patients With Lynch Syndrome. 两例Lynch综合征患者的错配修复熟练结肠腺癌。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-12-11 DOI: 10.1111/cge.14670

Binny Khandakar, Jill Lacy, Joanna A Gibson

引用次数: 0

Expanding the Clinical and Mutational Spectrum of Biallelic POC1A Variants: Characterization of Four Patients and a Comprehensive Review of POC1A-Related Phenotypes. 扩大双等位基因POC1A变异的临床和突变谱：4例患者的特征和POC1A相关表型的全面回顾。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-12-11 DOI: 10.1111/cge.14672

Umut Altunoglu, Gozde Tutku Turgut, Esin Karakılıç Özturan, Tuğba Kalaycı, Mert Kaya, Güven Toksoy, Firdevs Baş, Hülya Kayserili, Feyza Darendeliler

{"title":"Expanding the Clinical and Mutational Spectrum of Biallelic POC1A Variants: Characterization of Four Patients and a Comprehensive Review of POC1A-Related Phenotypes.","authors":"Umut Altunoglu, Gozde Tutku Turgut, Esin Karakılıç Özturan, Tuğba Kalaycı, Mert Kaya, Güven Toksoy, Firdevs Baş, Hülya Kayserili, Feyza Darendeliler","doi":"10.1111/cge.14672","DOIUrl":"https://doi.org/10.1111/cge.14672","url":null,"abstract":"SOFT syndrome (SOFTS) is an autosomal recessive disorder caused by biallelic POC1A variants, characterized by short stature, distinctive facial features, onychodysplasia, and hypotrichosis. To date, 21 pathogenic POC1A variants have been reported in 26 families. This study aims to broaden the phenotypic and genotypic spectrum of SOFTS with emphasis on the long-term effects of growth hormone (GH) therapy. We report four unrelated patients with three homozygous POC1A variants and demonstrate the transcriptional effects of two canonical splicing variants. All four patients had severe growth retardation, sparse hair/eyebrows, high/prominent forehead, long/triangular face, prominent nose, short middle/distal phalanges, puffy/tapering fingers, and prominent heels. Endocrine abnormalities included insulin resistance and impaired glucose tolerance, dyslipidemia, GH deficiency, central hypothyroidism, and precocious puberty. Two patients treated long-term with recombinant human GH showed insufficient responses. We also provide an extensive review of 43 cases including those we report, contributing to a better understanding of the full clinical and endocrinological spectrum of SOFTS.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling New Clinical and Genetic Insights in Ultra-Rare Intellectual Disability Phenotypes: A Study of a Turkish Cohort. 在超罕见智力残疾表型中揭示新的临床和遗传见解：一项土耳其队列研究。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-12-11 DOI: 10.1111/cge.14669

Ayberk Turkyilmaz, Safiye Gunes Sager, Kerem Terali, Pinar Ozkan Kart, Tulay Kamasak, Akif Ayaz, Alper Han Cebi, Ali Cansu

{"title":"Unveiling New Clinical and Genetic Insights in Ultra-Rare Intellectual Disability Phenotypes: A Study of a Turkish Cohort.","authors":"Ayberk Turkyilmaz, Safiye Gunes Sager, Kerem Terali, Pinar Ozkan Kart, Tulay Kamasak, Akif Ayaz, Alper Han Cebi, Ali Cansu","doi":"10.1111/cge.14669","DOIUrl":"https://doi.org/10.1111/cge.14669","url":null,"abstract":"Intellectual disability (ID) is defined as a severe impairment in reasoning, learning, and problem-solving abilities along with adaptive behavior that occurs before the age of 18 years. The present study aimed to present the clinical and genetic data of a cohort of Turkish pediatric patients diagnosed with the ultrarare (which only up to 20 cases having been reported in the relevant literature thus far) ID phenotype. A total of 29 patients from 26 different families, who were diagnosed with ultrarare ID upon whole exome sequencing (WES) analysis, were included in the study. Of the patients included in the study, 18 (62%) were male and 11 (38%) were female. There was consanguinity between parents in 16 families (55%). With respect to the ID phenotype, three families had cases with a similar phenotype, while 23 families (88%) had sporadic cases. Upon molecular analysis, 28 different variations in 23 different genes were noted. Of the variations detected, 15 were missense, 6 nonsense, 4 frameshift, 2 splice-site, and 1 gross exonic deletion. Nine (32%) variations were novel among the detected variations. This study summarized the clinical and genetic features of 23 different ultrarare ID phenotypes by means of WES study, including copy number variations (CNVs) analysis. Novel clinical and genetic findings in the present study contribute to a better understanding of the genotypic and phenotypic spectrum. The effects of some rare variations on protein structure were revealed by means of in silico modeling. Newly described cases with ultrarare phenotypes help achieve a clearer description of the clinical and genetic manifestations of the syndromes and gain a better understanding of the molecular mechanisms.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Split Hand-Foot Malformations-Unveiling Unique Molecular Diagnosis From a Brazilian Cohort. 拆分手脚畸形-揭示独特的分子诊断从巴西队列。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-12-08 DOI: 10.1111/cge.14666

Eduardo Da Cás, José Ricardo Magliocco Ceroni, Guilherme Lopes Yamamoto, Matheus Augusto Araújo Castro, Edgard França Bisneto, Alexander Augusto de Lima Jorge, Joao Bosco Oliveira Filho, Chong Ae Kim, Ana Cristina Vitorino Krepischi, Débora Romeo Bertola

{"title":"Split Hand-Foot Malformations-Unveiling Unique Molecular Diagnosis From a Brazilian Cohort.","authors":"Eduardo Da Cás, José Ricardo Magliocco Ceroni, Guilherme Lopes Yamamoto, Matheus Augusto Araújo Castro, Edgard França Bisneto, Alexander Augusto de Lima Jorge, Joao Bosco Oliveira Filho, Chong Ae Kim, Ana Cristina Vitorino Krepischi, Débora Romeo Bertola","doi":"10.1111/cge.14666","DOIUrl":"https://doi.org/10.1111/cge.14666","url":null,"abstract":"Split hand-foot malformation (SHFM) is a congenital limb malformation affecting primarily the central rays of the hands and/or feet, with variable expressivity, incomplete penetrance and syndromic forms. It is genetically heterogeneous, including point mutations and structural variants in different loci. Five individuals with SHFM were clinically evaluated in a Tertiary Center in Brazil: four of them presented additional, nonskeletal findings, including one individual with split foot, hand syndactyly, and ectodermal findings. Structural variants and point mutations in genes associated with SHFM were identified in all individuals. Our results highlight genetic heterogeneity observed in this group of skeletal disorders, alongside incomplete penetrance, a challenging task imposed on genetic counseling. Of note, an individual harboring a recurrent heterozygous variant in MAP3K20 presented a phenotype reminiscent of TP63-related disorders, contrary to the one recently reported in the literature with prominent facial dysmorphisms, expanding the phenotypic spectrum of this newly recognized syndromic form of SHFM.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0