Clinical Genetics最新文献_第2页

From Function to Mechanism: Unveiling the Role of Small Nucleolar Ribonucleic Acids in Digestive Tumours. 从功能到机制：揭示小核仁核糖核酸在消化道肿瘤中的作用。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-03-06 DOI: 10.1111/cge.14739

Dongxin Xi, Guli Shayila Dui Sanbai, Min Jiang, Zhihao Zhang, Taoran Sun, Weijia Wang, Yu Guo

{"title":"From Function to Mechanism: Unveiling the Role of Small Nucleolar Ribonucleic Acids in Digestive Tumours.","authors":"Dongxin Xi, Guli Shayila Dui Sanbai, Min Jiang, Zhihao Zhang, Taoran Sun, Weijia Wang, Yu Guo","doi":"10.1111/cge.14739","DOIUrl":"https://doi.org/10.1111/cge.14739","url":null,"abstract":"Small nucleolar ribonucleic acids (snoRNAs) have emerged as crucial regulators in various biological processes and have garnered significant attention for their potential roles in cancer. These noncoding ribonucleic acids (RNAs) primarily guide ribosomal RNA (rRNA) pseudouridylation and 2'-O-methylation modifications and exhibit stable expression in the serum, making them promising biomarkers and therapeutic targets. Digestive tract cancer poses a severe global health threat due to its high mortality rate and difficulty in early detection. Understanding the molecular mechanisms underlying tumor development is critical for improving diagnostic and therapeutic strategies. Small nucleolar RNAs, with their diverse functions and stable presence in biological fluids, offer a unique opportunity to address these challenges. Small nucleolar RNAs are a class of small noncoding RNAs mainly located in the nucleolus of eukaryotic cells. They play essential roles in the maturation and modification of rRNAs, transfer RNAs, and small nuclear RNAs. They also participate in alternative splicing regulation and exhibit microRNA-like functions, influencing various cellular processes. Abnormal expression of snoRNAs has been closely linked to the development, invasion, and metastasis of digestive system tumors. Given their stable expression in serum and the ability to function independently of host genes, snoRNAs hold great potential as biomarkers for early screening, prognosis prediction, and therapeutic targets in digestive system tumors. Their involvement in key signaling pathways and molecular mechanisms provides a foundation for developing targeted therapies and improving patient outcomes. This review highlights the significance of snoRNAs in digestive system tumors, their biological roles, connections to cancer progression, and potential clinical applications. Further exploration of snoRNAs is expected to provide new insights into the diagnosis and treatment of digestive system tumors.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572431","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

Impact of SDHA Mutations on Yeast Growth and Mitochondrial Function. Case Study Linking Genetic Findings to Clinical Phenotypes. SDHA 基因突变对酵母生长和线粒体功能的影响。将基因发现与临床表型联系起来的案例研究。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-03-06 DOI: 10.1111/cge.14738

Camilla Meossi, Alessandro De Falco, Marco Marchi, Anna Rubegni, Stefano Pagano, Rosanna Trovato, Claudia Nesti, Flavio Dal Canto, Emanuele Bartolini, Leonardo Salviati, Filippo Maria Santorelli

引用次数: 0

Limited Diagnostic Utility of PRDM10 Analysis in Birt-Hogg-Dubé Syndrome: Experience in 313 Consecutive Patients. PRDM10分析在birt - hogg - dub<s:1>综合征中的有限诊断效用：313例连续患者的经验

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-03-03 DOI: 10.1111/cge.14737

Agathe Hercent, Ibrahima Ba, Dimitri Tchernitchko

引用次数: 0

NEUROMYODredger: Whole Exome Sequencing for the Diagnosis of Neurodevelopmental and Neuromuscular Disorders in Seven Countries. NEUROMYODredger：全外显子组测序诊断七个国家的神经发育和神经肌肉疾病。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-25 DOI: 10.1111/cge.14736

Edoardo Malfatti, Alexandru Caramizaru, Hane Lee, JiHye Kim, Hussein Shoaito, Alessandra Pennisi, Sarah Souvannanorath, François-Jérôme Authier, Andreea Dumitrescu, Nagia Fahmy, Rosa Elena Escobar-Cedillo, Antonio Miranda-Duarte, Alexandra Berenice Luna-Angulo, Sonia Nouioua, Ouissem Benchaabi, Meriem Tazir, Sihem Hallal, Peggy Martinez, Claudia Castiglioni, Amelia Dobrescu, Homa Tajsharghi

{"title":"NEUROMYODredger: Whole Exome Sequencing for the Diagnosis of Neurodevelopmental and Neuromuscular Disorders in Seven Countries.","authors":"Edoardo Malfatti, Alexandru Caramizaru, Hane Lee, JiHye Kim, Hussein Shoaito, Alessandra Pennisi, Sarah Souvannanorath, François-Jérôme Authier, Andreea Dumitrescu, Nagia Fahmy, Rosa Elena Escobar-Cedillo, Antonio Miranda-Duarte, Alexandra Berenice Luna-Angulo, Sonia Nouioua, Ouissem Benchaabi, Meriem Tazir, Sihem Hallal, Peggy Martinez, Claudia Castiglioni, Amelia Dobrescu, Homa Tajsharghi","doi":"10.1111/cge.14736","DOIUrl":"https://doi.org/10.1111/cge.14736","url":null,"abstract":"Although substantial advancements have been made in genetic testing, several barriers continue to limit patient access, leading to delays in diagnosis, effective treatments, and preventative measures. The NEUROMYODredger-3billion Megaproject End the Diagnostic Odyssey grant offered free whole exome sequencing (WES) to 245 patients with undiagnosed neurodevelopmental or neuromuscular disorders in seven countries: Algeria, Chile, Egypt, France, Mexico, Peru, and Romania. We found pathogenic variants in 79 patients (diagnostic yield 32.24%)-36 neurodevelopmental (43.90%) and 43 neuromuscular (26.38%). Fifty patients harboured variants of uncertain significance (VUS, 20.40%)-14 neurodevelopmental (17.07%) and 36 neuromuscular (22.08%), and 116 patients had negative results (47.34%). NEUROMYODredger helped end the diagnostic odyssey in around 30% of patients, while ongoing functional studies and reanalysis strategies are used in order to reach more diagnoses. In conclusion, a singleton WES approach is valuable in determining the genetic diagnosis of neurodevelopmental and neuromuscular diseases, especially in low and middle-income countries.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499442","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

A Novel UPF1 Variant Associated With a Rare UPF1-Related Neurodevelopmental Disorder. 一种新的UPF1变异与罕见的UPF1相关神经发育障碍相关。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-24 DOI: 10.1111/cge.14735

Zeynep Tümer, Jonas Dalsberg, Gitte Rønde, Jesper Kiehn Sørensen, Elsebet Østergaard

{"title":"A Novel UPF1 Variant Associated With a Rare UPF1-Related Neurodevelopmental Disorder.","authors":"Zeynep Tümer, Jonas Dalsberg, Gitte Rønde, Jesper Kiehn Sørensen, Elsebet Østergaard","doi":"10.1111/cge.14735","DOIUrl":"https://doi.org/10.1111/cge.14735","url":null,"abstract":"Nonsense-mediated mRNA decay (NMD) plays a crucial role in degrading aberrant transcripts with premature termination codons, with the Up-frameshift (UPF) protein family-UPF1, UPF2, and UPF3A/UPF3B-being vital components of this machinery. While several variants in genes encoding UPF2 and UPF3A/3B have been associated with neurodevelopmental disorders, only three germline UPF1 variants have been reported to date. Here, we report a male patient with a de novo missense variant, p.(Ala526Thr), in a highly conserved helicase motif of UPF1. The patient presented with moderate intellectual disability (ID), atypical autism, attention deficit hyperactivity disorder (ADHD), and behavioral disturbances. The common features observed among the four patients with UPF1 variants are moderate to severe ID and developmental delays in motor and verbal skills. A comparison across the disorders related to the UPF genes suggests that neurodevelopmental delay, including ID and impaired verbal skills, is a common feature, and these disorders may collectively be referred to as UPF-related neurodevelopmental disorders (NDDs). ADHD, autism, seizures, hypotonia, and non-specific dysmorphic features are also reported in some patients, suggesting that these disorders can be classified as non-specific intellectual disability syndromes. However, further studies are necessary to elucidate genotype-phenotype correlations and the molecular mechanisms underlying these rare disorders, particularly those related to UPF1.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491101","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

Transcript Long-Read Sequencing Unveils the Molecular Complexity of a Novel ROGDI Splicing Variant in a Tunisian Family With Kohlschütter-Tönz Syndrome. 转录本长读测序揭示了突尼斯Kohlschütter-Tönz综合征家族中新的ROGDI剪接变异的分子复杂性。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-24 DOI: 10.1111/cge.14725

Miriam Essid, Sana Karoui, Mouna Zribi, Thouraya Ben Younes, Louis Januel, Estelle Lafont, Audrey Labalme, Meriem Ben Hafsa, Go Hun Seo, Safa Khatrouch, Hela Boudabous, Amel Ben Chehida, Damien Sanlaville, Houweyda Jilani, Lamia Benjemaa, Ichraf Kraoua, Gaetan Lesca, Nicolas Chatron

{"title":"Transcript Long-Read Sequencing Unveils the Molecular Complexity of a Novel ROGDI Splicing Variant in a Tunisian Family With Kohlschütter-Tönz Syndrome.","authors":"Miriam Essid, Sana Karoui, Mouna Zribi, Thouraya Ben Younes, Louis Januel, Estelle Lafont, Audrey Labalme, Meriem Ben Hafsa, Go Hun Seo, Safa Khatrouch, Hela Boudabous, Amel Ben Chehida, Damien Sanlaville, Houweyda Jilani, Lamia Benjemaa, Ichraf Kraoua, Gaetan Lesca, Nicolas Chatron","doi":"10.1111/cge.14725","DOIUrl":"https://doi.org/10.1111/cge.14725","url":null,"abstract":"Kohlschütter-Tönz Syndrome (KTS) is an ultra-rare autosomal recessive disorder, characterized by a clinical triad: infantile-onset epilepsy, global developmental delay, and amelogenesis imperfecta. KTS is caused by pathogenic variants in ROGDI, encoding a leucine zipper protein of unknown function. Our study characterizes a novel homozygous ROGDI variant (NM_024589.3:c.646-2A>G) identified in a Tunisian family case with KTS, renal tubular acidosis, and hyperammonemia. This variant disrupts a canonical acceptor splice site (ASS) in intron 8. Reverse-transcriptase polymerase chain reaction and targeted long-read cDNA sequencing, identified only abnormal transcripts secondary to the ROGDI ASS variant in the proband. Complex splicing events were detected including exon 9 skipping, cryptic ASS activation leading to 13-bp deletion in exon 9, and retention of intron 8 or both intron 8 and 9. These alterations were all predicted to result in nonsense mediated decay and ROGDI loss of function. By integrating complementary techniques, our study unveiled fundamental mechanisms underlying complex splice alterations, providing insights that may guide future therapeutic strategies in KTS.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491194","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

A Novel RHEB Germline Variant Associated With Intellectual Disability and Epilepsy: Expanding the Spectrum of mTORopathies. 与智力残疾和癫痫相关的一种新的RHEB种系变异：扩大了肿瘤的范围。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-24 DOI: 10.1111/cge.14734

Juan Pablo Trujillo-Quintero, Anna Brunet-Vega, Nino Spataro, Joan Petanas, Oriol Gallego, Francesca Mateo, Miquel Angel Pujana, Anna Ruiz

引用次数: 0

Loss of Function SPTAN1 Variants Result in Ataxia and Intellectual Disability.

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-23 DOI: 10.1111/cge.14732

Po-Nien Lu, Chandler Melton, Barbara Dupont, Julie R Jones, Fatima Abidi, Aubrey Rose, Wesley G Patterson, Michael J Lyons, Heather Flanagan-Steet

{"title":"Loss of Function SPTAN1 Variants Result in Ataxia and Intellectual Disability.","authors":"Po-Nien Lu, Chandler Melton, Barbara Dupont, Julie R Jones, Fatima Abidi, Aubrey Rose, Wesley G Patterson, Michael J Lyons, Heather Flanagan-Steet","doi":"10.1111/cge.14732","DOIUrl":"https://doi.org/10.1111/cge.14732","url":null,"abstract":"SPTAN1 mutations have been reported in association with autosomal dominant early infantile epileptic encephalopathy 5. Individuals present with early-onset seizures and profound intellectual disability. Recent reports suggest a wider spectrum with later-onset seizures and milder developmental delay. Here we describe two patients with loss-of-function variants in SPTAN1. One patient has ataxia and mild intellectual disability stemming from a de novo homozygous p.(Gln1448Pro) variant associated with uniparental disomy 9. The second patient, carrying a heterozygous p.(Asn1839del) allele, exhibits more substantial motor issues, developmental delay, and seizures. Ectopically expressed wild-type or variant-containing forms of sptan1 in zebrafish indicate both variants create loss-of-function alleles, with the p.(Gln1448Pro) likely being hypomorphic. This conclusion is supported by reduced protein abundance and localization of Sptan1 variants in axons of developing embryos. Further, unlike wild-type sptan1, analysis of the p.(Gln1448Pro) variant showed it failed to restore voltage-gated sodium channel localization in sptan1-null axons. Additional behavioral analyses show supplementation with the amino acid D-aspartate improved motility in sptan1-null zebrafish, supporting its use for α-II spectrin-associated motor dysfunction.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482285","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

A Novel Missense Mutation in SLC12A6 Impairs Ion Transport Function of the Protein to Cause Agenesis of the Corpus Callosum With Peripheral Neuropathy. 一种新的SLC12A6错义突变损害了该蛋白的离子转运功能，导致胼胝体发育不全伴周围神经病变。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-23 DOI: 10.1111/cge.14733

S Rehan Ahmad, Saema Hanafi

{"title":"A Novel Missense Mutation in SLC12A6 Impairs Ion Transport Function of the Protein to Cause Agenesis of the Corpus Callosum With Peripheral Neuropathy.","authors":"S Rehan Ahmad, Saema Hanafi","doi":"10.1111/cge.14733","DOIUrl":"https://doi.org/10.1111/cge.14733","url":null,"abstract":"Agenesis of the corpus callosum with peripheral neuropathy (ACCPN) is a rare autosomal recessive disorder characterized by malformation or absence of the corpus callosum, accompanied by progressive peripheral nerve degeneration. ACCPN is associated with mutations in the SLC12A6 gene, encoding the potassium-chloride cotransporter (also termed KCC3), which plays a crucial role in neuronal ion homeostasis. In this study, we report a novel homozygous missense variant (c.1634A>G, p.H371R) in SLC12A6, identified through exome sequencing in a male proband presenting with ACCPN symptoms, including developmental delay, hypotonia, epileptic seizures, and corpus callosal dysgenesis. The proband's MRI findings revealed additional neurodevelopmental abnormalities such as hippocampal malformation. Functional analysis showed that while the mutant SLC12A6 transcript and protein levels were comparable to wild type, the mutant protein was mislocalized to the cytoplasm, disrupting its ion transport function. This mislocalization caused an imbalance in potassium and chloride ion levels in the proband's cells. Bioinformatics tools predicted the pathogenicity of the p.H371R mutation, and structural modeling revealed a destabilization effect. Elevated levels of cellular senescence markers, p16 and p21, were detected, indicating that ion dysregulation due to SLC12A6-p.H371R mislocalization contributed to cellular stress. This study provides novel insights into the pathogenic mechanism of ACCPN, highlighting the importance of mutant SLC12A6 mislocalization and ion homeostasis in disease progression. The identification of the p.H371R mutation adds to the spectrum of SLC12A6 mutations linked to ACCPN and underscores the potential for targeted therapeutic strategies.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482284","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

Case Series of Eight Congenital Tufting Enteropathy Patients and Literature Review.

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-20 DOI: 10.1111/cge.14702

Youhong Fang, Youyou Luo, Luojia Xu, Jindan Yu, Jie Chen

{"title":"Case Series of Eight Congenital Tufting Enteropathy Patients and Literature Review.","authors":"Youhong Fang, Youyou Luo, Luojia Xu, Jindan Yu, Jie Chen","doi":"10.1111/cge.14702","DOIUrl":"https://doi.org/10.1111/cge.14702","url":null,"abstract":"Congenital tufting enteropathy (CTE) is a rare autosomal recessive inherited disorder caused by mutations in the epithelial cell adhesion molecule (EpCAM) gene, characterized by severe diarrhea and growth failure. Between December 2017 and December 2023, eight patients diagnosed with CTE at our hospital were retrospectively analyzed for their clinical and genetic features, alongside a comprehensive literature review. All patients presented with severe malnutrition and growth failure upon admission. Parenteral nutrition (PN) with high caloric intake was required for all patients to achieve growth catch-up. A total of 142 patients with EpCAM mutations were reviewed, including 137 previously reported cases and five newly identified patients described in this study. Among the 114 CTE patients with detailed treatment information, 108 patients received PN therapy, with six patients successfully weaned off PN. Additionally, 19 patients underwent intestinal transplantation (IT). Outcome analysis revealed that 30 patients (27.3%) died, including five post-IT deaths. A total of 68 EpCAM mutations were identified, with most located in exon 3. The most frequently reported variant was c.499dup C. In this study, four novel mutations were detected in our patients. This study provides a comprehensive overview of the clinical and genetic characteristics of CTE, enhancing the understanding of its phenotype and genotype, particularly in Asian patients.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467227","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