Clinical Genetics最新文献_第4页

A Homozygous Frameshift Variant in KHDC4 Is Associated With a Syndromic Inherited Retinal Disease in Humans. KHDC4纯合子移码变异与人类综合征遗传性视网膜疾病相关

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-09-30 DOI: 10.1111/cge.70256

Asodu Sandeep Sarma, Neta Barnoy, Prakadeeswari Gopalakrishnan, Keren Dichter, Rotem Mizrachi, Manar Salameh, Eyal Banin, Dror Sharon, Adi Inbal, Samer Khateb

引用次数: 0

Müllerian Duct Aplasia in a Girl With SMARCB1-Related Coffin-Siris Syndrome: A Rare Co-Occurring Anomaly. 患有smarcb1相关的Coffin-Siris综合征的女孩的<s:1> lererian导管发育不全：一种罕见的共同发生的异常。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-09-28 DOI: 10.1111/cge.70257

Anneli C S Bolund, Esben Thyssen Vestergaard, Edvard Marinovskij, Dorte Launholt Lildballe, Jenny Blechingberg, Morten Krogh Herlin

{"title":"Müllerian Duct Aplasia in a Girl With SMARCB1-Related Coffin-Siris Syndrome: A Rare Co-Occurring Anomaly.","authors":"Anneli C S Bolund, Esben Thyssen Vestergaard, Edvard Marinovskij, Dorte Launholt Lildballe, Jenny Blechingberg, Morten Krogh Herlin","doi":"10.1111/cge.70257","DOIUrl":"https://doi.org/10.1111/cge.70257","url":null,"abstract":"Genetic etiologies of Müllerian aplasia (Mayer-Rokitansky-Küster-Hauser syndrome) remain poorly understood. Identification of patients with monogenic syndromes presenting with Müllerian aplasia may help improve our knowledge of the underlying biology. We investigated a 15-year-old female presenting with primary amenorrhea due to Müllerian aplasia, dysmorphic features, and intellectual disability. Trio whole genome sequencing identified a pathogenic de novo missense variant in NM_003073.5(SMARCB1): c.1096C>T, p.(Arg366Cys) confirming the diagnosis of Coffin-Siris syndrome 3 (OMIM #614608). This patient represents the first molecularly confirmed case of Coffin-Siris syndrome presenting with Müllerian aplasia; however, two previous clinical reports support this potential rare association. Research is needed to further investigate this possible association, determine the prevalence of Müllerian aplasia in adolescent/adult female patients with Coffin-Siris syndrome and whether it may be associated with other BAF (BRG1/BRM-associated factor) complex genes than SMARCB1. Finally, it is unknown how BAF complex dysfunction may be involved in perturbed Müllerian duct development in females.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073666","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

Liquid Biopsy and Multi-Cancer Early Detection Tests for Cancer Screening: A Scoping Review. 液体活检和多种癌症早期检测试验用于癌症筛查：范围综述。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-09-25 DOI: 10.1111/cge.70249

Tessa Robinson, Marian Saab, Lily Thao Nguyen, Pooja Kochar, Olivia Meggetto, Jill Tinmouth, Meghan J Walker

{"title":"Liquid Biopsy and Multi-Cancer Early Detection Tests for Cancer Screening: A Scoping Review.","authors":"Tessa Robinson, Marian Saab, Lily Thao Nguyen, Pooja Kochar, Olivia Meggetto, Jill Tinmouth, Meghan J Walker","doi":"10.1111/cge.70249","DOIUrl":"https://doi.org/10.1111/cge.70249","url":null,"abstract":"Liquid biopsy constitutes a range of tests that use biological fluids to detect cancer. Research is now targeting their use for cancer screening. This is the first review of the evidence on liquid biopsy tests across a range of analytical parameters, biomarkers, and cancer types for cancer screening. A scoping review was conducted using JBI methodology for scoping reviews. MEDLINE and targeted websites were searched for studies published in 2014 or later on the use of liquid biopsy and multi-cancer early detection tests for screening. A total of 104 studies were included, covering a wide range of study designs. Several types of biomarkers (e.g., cell-free DNA, circulating tumor DNA) and analytical parameters were used. Most studies addressed test performance outcomes, while fewer addressed clinical outcomes, implementation considerations, and cost-effectiveness. No empirical studies on cancer-specific mortality were found. A large body of literature was identified that covered a range of cancer types, biomarkers, analytical parameters, and outcomes. Critical gaps in the literature were demonstrated, including evidence on clinical outcomes such as cancer-specific mortality and potential harms that currently preclude the implementation of liquid biopsy tests for cancer screening. Findings of this review can be used to guide the necessary future research.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058709","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

Deep Phenotyping in ReNU Syndrome Identifies a Recognizable Age-Dependent Clinical Trajectory. ReNU综合征的深度表型确定了可识别的年龄依赖性临床轨迹。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-09-25 DOI: 10.1111/cge.70252

Nadja Pekkola Pacheco, Malin Kvarnung, Anna Hammarsjö, Daniel Nilsson, Bianca Tesi, Britt Marie Anderlid, Giedre Grigelioniene, Maria Johansson Soller, Liselot van der Laan, Charlotte Willfors, Charlotta Ingvoldstad Malmgren, Anna Lindstrand, Tommy Stödberg, Ann Nordgren, Angelica Maria Delgado-Vega

{"title":"Deep Phenotyping in ReNU Syndrome Identifies a Recognizable Age-Dependent Clinical Trajectory.","authors":"Nadja Pekkola Pacheco, Malin Kvarnung, Anna Hammarsjö, Daniel Nilsson, Bianca Tesi, Britt Marie Anderlid, Giedre Grigelioniene, Maria Johansson Soller, Liselot van der Laan, Charlotte Willfors, Charlotta Ingvoldstad Malmgren, Anna Lindstrand, Tommy Stödberg, Ann Nordgren, Angelica Maria Delgado-Vega","doi":"10.1111/cge.70252","DOIUrl":"https://doi.org/10.1111/cge.70252","url":null,"abstract":"Pathogenic variants in the noncoding gene RNU4-2 cause ReNU syndrome, a common neurodevelopmental disorder. Although the core phenotype is well described, longitudinal symptom progression and family perspectives remain insufficiently characterized. We identified 11 individuals with RNU4-2 pathogenic variants through reanalysis of clinical whole genome sequencing (WGS) data from a previously undiagnosed cohort. Using deep phenotyping, including retrospective medical record review and parental insights, we delineated a recognizable age-dependent clinical trajectory. Infancy was characterized by feeding difficulties, hypotonia, decelerating head growth, and visual abnormalities; early childhood by gait disturbances, autistic behavior, and seizure onset; and later childhood by persistent severe speech impairment with emerging orthopedic complications. Notably, feeding problems and seizures improved over time in several individuals. Core features included developmental delay, intellectual disability, speech abnormalities, hypotonia, autism, postnatal growth retardation, visual and brain abnormalities, and similar facial features. Parents emphasized strong social connectedness and affection and often described infancy as the most challenging stage due to feeding difficulties and failure to thrive. This study refines the natural history of ReNU syndrome and provides guidance for clinical management and counselling. It also highlights the value of routine WGS reanalysis as novel disease genes are identified.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058717","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

Loss-Of-Function CCM Gene Variants in Japanese Patients With Cerebral Cavernous Malformations. 日本脑海绵状血管病患者功能缺失的CCM基因变异

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-09-24 DOI: 10.1111/cge.70253

Takahiro Hori, Satoshi Tsutsumi, Kazutoshi Hashimoto, Taichi Ishiguro, Hidenori Ohbuchi, Yasunaga Yamamoto, Emi Nomura, Kenko Azuma, Yuichi Kubota, Hiroyuki Akagawa

{"title":"Loss-Of-Function CCM Gene Variants in Japanese Patients With Cerebral Cavernous Malformations.","authors":"Takahiro Hori, Satoshi Tsutsumi, Kazutoshi Hashimoto, Taichi Ishiguro, Hidenori Ohbuchi, Yasunaga Yamamoto, Emi Nomura, Kenko Azuma, Yuichi Kubota, Hiroyuki Akagawa","doi":"10.1111/cge.70253","DOIUrl":"10.1111/cge.70253","url":null,"abstract":"Hereditary cerebral cavernous malformations (CCMs) are characterized by lesion multiplicity and the formation of de novo lesions, in contrast to sporadic forms. We performed sequencing analyses covering the known autosomal dominant loci CCM1/KRIT1, CCM2/CCM2 (Malcavernin), and CCM3/PDCD10 in 11 patients from eight families with CCMs. All patients had multiple lesions, and de novo lesions were observed in four patients (36.4%). Heterozygous loss-of-function variants were identified in seven families, including four variants of KRIT1, two of CCM2, and one of PDCD10. Among them, c.1730 + 4_1730 + 7delAGTA in KRIT1 and c.609G>A (p.Lys203=) in CCM2 were putative splicing variants located outside the invariant GT/AG dinucleotides at the splice junction because AI-based prediction tools indicated that both variants may disrupt normal splicing. In vitro splicing assays confirmed that the AI-based predictions were correct, and the same aberrant splicing pattern was reproduced by reverse transcription PCR using tissue-derived RNA for the c.609G>A variant in CCM2. In one patient with numerous CCM lesions, whole-genome sequencing was performed, which showed no abnormalities in the three known CCM loci, including deep intronic and structural variants. This may indicate the technological limitations of current bioinformatics analyses or the presence of a novel CCM gene.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036841","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 New Case of Lethal Congenital Contracture Syndrome Type 3 With Hyperinsulinism and Optic Atrophy. 致死性先天性挛缩综合征3型伴高胰岛素血症及视神经萎缩1例。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-09-16 DOI: 10.1111/cge.70231

Tameemi Abdalla Moady, Hadar Hulin Ma'ayan, Michal Cohen, Karin Weiss

{"title":"A New Case of Lethal Congenital Contracture Syndrome Type 3 With Hyperinsulinism and Optic Atrophy.","authors":"Tameemi Abdalla Moady, Hadar Hulin Ma'ayan, Michal Cohen, Karin Weiss","doi":"10.1111/cge.70231","DOIUrl":"https://doi.org/10.1111/cge.70231","url":null,"abstract":"Lethal congenital contracture syndrome 3 (LCCS3, MIM #611369) is a rare autosomal recessive neuromuscular disorder caused by biallelic loss-of-function (LOF) variants in PIP5K1C, reported in only two families to date. It typically presents with severe fetal akinesia, arthrogryposis multiplex congenita, and perinatal lethality due to respiratory insufficiency case. Herein, we report a new case with survival beyond birth. Prenatal findings included clubfeet with preserved amniotic fluid volume and fetal movements. The infant was delivered by cesarean section at 37 + 7 weeks following breech presentation and developed respiratory distress requiring 14 days of ventilatory support. Physical examination revealed bilateral talipes equinovarus, flexion contractures of the knees, restricted hip mobility, clenched hands with flexion contractures of the third and fourth fingers, and hyperextension of the second and fifth fingers. Neurologically, he had encephalopathy, profound hypotonia with a frog posture, and abnormal neonatal reflexes with a discontinuous background pattern on cerebral function monitoring. Additional observed features were bilateral optic atrophy and hyperinsulinemic hypoglycemia responsive to Diazoxide. Trio genome sequencing identified a homozygous pathogenic splice-site variant in PIP5K1C (c.1127+1G>A, NM_012398.3). The infant died at 6 months from multisystemic failure. Further studies are warranted to elucidate the pathomechanisms underlying the PIP5K1C defect and its phenotypic consequences.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975636","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

Genetic Spectrum of Cholestasis in Tunisia and Diagnostic Yield of Next-Generation Sequencing: Case Series of 70 Patients. 突尼斯胆汁淤积症的遗传谱和新一代测序的诊断率：70例患者的病例系列。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-09-15 DOI: 10.1111/cge.70242

Amal Abdmouleh, Houweyda Jilani, Imen Rejeb, Syrine Hizem, Nicolas Pottier, Romain Larrue, Wendy Arondal, Lucie Hanquet, Rania Benrabeh, Olfa Bouyahia, Sonia Mazigh, Yasmina Elaribi, Lamia Benjemaa

{"title":"Genetic Spectrum of Cholestasis in Tunisia and Diagnostic Yield of Next-Generation Sequencing: Case Series of 70 Patients.","authors":"Amal Abdmouleh, Houweyda Jilani, Imen Rejeb, Syrine Hizem, Nicolas Pottier, Romain Larrue, Wendy Arondal, Lucie Hanquet, Rania Benrabeh, Olfa Bouyahia, Sonia Mazigh, Yasmina Elaribi, Lamia Benjemaa","doi":"10.1111/cge.70242","DOIUrl":"https://doi.org/10.1111/cge.70242","url":null,"abstract":"Cholestasis is caused by genetic disorders in 25% of cases. Our study aimed to describe the clinical and genetic profile of cholestasis and to demonstrate the importance of next-generation sequencing (NGS) in the etiologic diagnosis of genetic cholestasis. We included patients referred for cholestasis over a 10-year period. Molecular studies using NGS consisted of a 292-gene panel and/or whole exome sequencing. Our cohort included 70 patients from 66 unrelated families. A genetic diagnosis was established in 70% of the families. The most common diagnoses were Type 2 progressive familial intrahepatic cholestasis (n = 12), neonatal sclerosing cholangitis (n = 4), low phospholipid-associated cholelithiasis syndrome (n = 4), and Alagille syndrome (n = 4). The ABCB11 gene was most frequently mutated (15/46), with two recurrent variants, c.1062T>A (p.Tyr354*) and c.1826_1827dup (p.Ile610Glnfs*45), found in six and four families, respectively. Our results showed a 62% diagnostic yield of molecular testing using NGS in cholestasis. An accurate diagnosis was key to providing appropriate genetic counseling, guiding screening of variant carriers, and prenatal diagnosis.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966919","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

Childhood-Onset Filamin c Related Cardiomyopathy: Genotype-Phenotype Correlation and Outcome. 儿童期发病的丝蛋白c相关心肌病：基因型-表型相关性和结果

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-09-13 DOI: 10.1111/cge.70248

Evelien Cansse, Wannes Renders, Luc Bruyndonckx, Bert Callewaert, Katya De Groote, Ruth Heying, Jelena Hubrechts, Stéphane Moniotte, Thomas Salaets, Laura Muiño Mosquera

{"title":"Childhood-Onset Filamin c Related Cardiomyopathy: Genotype-Phenotype Correlation and Outcome.","authors":"Evelien Cansse, Wannes Renders, Luc Bruyndonckx, Bert Callewaert, Katya De Groote, Ruth Heying, Jelena Hubrechts, Stéphane Moniotte, Thomas Salaets, Laura Muiño Mosquera","doi":"10.1111/cge.70248","DOIUrl":"https://doi.org/10.1111/cge.70248","url":null,"abstract":"Filamin C (FLNC) contributes to 1%-8% of adult-onset cardiomyopathy (CMP), with a high prevalence of end-stage heart failure and sudden cardiac death, particularly for FLNC truncating variants (FLNCtv), rendering it one of the high-risk CMP genes. Outcome data and genotype-phenotype correlation in children are scarce. We conducted a retrospective cohort study of children (< 18 years) with CMP features and a (likely) pathogenic FLNC variant, identified via literature search or in the Belgian Pediatric Cardiology Registry (BePCaR), to evaluate cardiovascular outcomes and genotype-phenotype correlations. Seventy-four individuals (56.8% male, median age 4.5 years) from 57 families were included. Restrictive CMP was the most prevalent phenotype. Half of the patients experienced major adverse cardiovascular events, including heart transplantation (20.3%) and death (13.5%). Hypertrophic CMP was exclusively associated with ROD2 domain variants. Mortality was significantly higher in FLNCtv carriers versus non-truncating carriers (26.9% vs. 6.3%, p = 0.019), and multivariate analysis identified FLNCtv as an independent predictor of adverse outcome (OR = 6.4, 95% CI: [1.36, 29.80]). Extracardiac manifestations occurred in 32.4%, predominantly in RCM patients, with myopathy-associated variants clustering in exons 21 and 41. Pathogenic FLNC variants associate with early-onset CMP and poor prognosis, underscoring the need for early genetic screening, risk stratification, and personalized follow-up to improve outcome.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963209","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 Homozygous Variant in DMRTB1 Is Associated With Non-Obstructive Azoospermia in Humans. DMRTB1基因的纯合子变异与人类非阻塞性无精子症有关。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-09-13 DOI: 10.1111/cge.70243

YuHang Li, Shuai Lu, Xun Wang, YiSong Ju, HaoQiang Zhang, Wen Yu, Liang Shi, Qihan Chen, Ao Ma, Xiaozhi Zhao

{"title":"A Homozygous Variant in DMRTB1 Is Associated With Non-Obstructive Azoospermia in Humans.","authors":"YuHang Li, Shuai Lu, Xun Wang, YiSong Ju, HaoQiang Zhang, Wen Yu, Liang Shi, Qihan Chen, Ao Ma, Xiaozhi Zhao","doi":"10.1111/cge.70243","DOIUrl":"https://doi.org/10.1111/cge.70243","url":null,"abstract":"Non-obstructive azoospermia (NOA) represents the most severe form of male infertility, and the pathogenesis in partial patients can be attributed to endocrine dysfunction or heritable genetic variants. Although the application of whole-exome sequencing (WES) has facilitated the identification of numerous pathogenic genes associated with NOA, the genetic etiology of a significant proportion of cases remains elusive. In this study, we identified an NOA patient carrying a novel variant in DMRTB1 (c.792-797del, p.265-266del). The variant was rare in public databases and predicted to be likely pathogenic according to the American College of Medical Genetics (ACMG) guidelines. Structural modeling performed by SWISS-MODEL revealed the localized structural perturbations within residues 254-266, which may induce functional alterations. Histological analysis (H&E staining) of the testicular tissue revealed a complete absence of mature sperm within the seminiferous tubules, which is consistent with the essential role of this gene demonstrated in Dmrt6 knockout mice. Our findings demonstrate that the identified DMRTB1 variant is closely associated with the pathogenesis of NOA, thereby providing valuable genetic evidence for the diagnosis of NOA.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963214","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

Genetic Testing Unveils a Novel Thrombospondin-1 Domain Containing Protein 1 Gene Variant as the Cause of Chronic Edema in a 79-Year-Old Woman. 基因检测揭示了一种新的血栓反应蛋白-1结构域含有蛋白1基因变异是79岁女性慢性水肿的原因。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-09-09 DOI: 10.1111/cge.70247

Eiko Amo, Takafumi Toyohara, Naoya Saijo, Satoko Sato, Jun Takayama, Yoshiko Suto, Yuji Noguchi, Sosuke Kinomura, Yusuke Ishizuka, Shun Watanabe, Koichi Kikuchi, Rui Makino, Mai Yoshida, Yuji Oe, Tasuku Nagasawa, Koji Okamoto, Takehiro Suzuki, Mariko Miyazaki, Shinya Kawaguchi, Takashi Suzuki, Takaaki Abe, Shigeo Kure, Atsuo Kikuchi, Tetsuhiro Tanaka

{"title":"Genetic Testing Unveils a Novel Thrombospondin-1 Domain Containing Protein 1 Gene Variant as the Cause of Chronic Edema in a 79-Year-Old Woman.","authors":"Eiko Amo, Takafumi Toyohara, Naoya Saijo, Satoko Sato, Jun Takayama, Yoshiko Suto, Yuji Noguchi, Sosuke Kinomura, Yusuke Ishizuka, Shun Watanabe, Koichi Kikuchi, Rui Makino, Mai Yoshida, Yuji Oe, Tasuku Nagasawa, Koji Okamoto, Takehiro Suzuki, Mariko Miyazaki, Shinya Kawaguchi, Takashi Suzuki, Takaaki Abe, Shigeo Kure, Atsuo Kikuchi, Tetsuhiro Tanaka","doi":"10.1111/cge.70247","DOIUrl":"https://doi.org/10.1111/cge.70247","url":null,"abstract":"Edema requires management tailored to its underlying etiology; however, in some cases the cause remains elusive. We describe a 79-year-old woman with lifelong unexplained peripheral edema. Comprehensive evaluation excluded common etiologies such as heart failure, renal dysfunction, and venous thrombosis. Whole-genome sequencing identified a novel homozygous splice-site variant (NM_018676.4:c.58+2T>G) in the thrombospondin-1 domain-containing protein 1 (THSD1) gene, which has previously been associated with non-immune hydrops fetalis (NIHF). This report describes, to our knowledge, the first elderly patient with chronic peripheral edema harboring a likely pathogenic THSD1 variant, suggesting that THSD1-related disease may, in rare instances, persist beyond the perinatal period and present into late adulthood. Although causality cannot be established definitively from a single case, the findings highlight the potential utility of genetic testing in adults with chronic unexplained edema.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910846","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