Human Genome Variation最新文献_第2页

Recurrent MBTPS2 variant c.970+5G>A in IFAP syndrome: a mutational hotspot. IFAP综合征复发性MBTPS2变异体c.970+5G>A：突变热点

IF 1.3

Human Genome Variation Pub Date : 2026-04-14 DOI: 10.1038/s41439-026-00346-2

Sheetal Kumar, Sohail Ahmed, Pietro Incardona, Nicole Cesarato, Yue Zhang, Monica Ines Natale, Muhammad Javed Khan, Laura Valinotto, Kifayat Ullah, Wasim Ahmad, Ines Irurzun, Peter M Krawitz, Bo Liang, Regina C Betz

引用次数: 0

ChatTogoVar: a TogoVar-based retrieval-augmented generation system for precise genomic variant interpretation. ChatTogoVar：一个基于togovar的检索增强代系统，用于精确的基因组变异解释。

IF 1.3

Human Genome Variation Pub Date : 2026-04-09 DOI: 10.1038/s41439-026-00344-4

Nobutaka Mitsuhashi, Toyofumi Fujiwara, Atsuko Yamaguchi

{"title":"ChatTogoVar: a TogoVar-based retrieval-augmented generation system for precise genomic variant interpretation.","authors":"Nobutaka Mitsuhashi, Toyofumi Fujiwara, Atsuko Yamaguchi","doi":"10.1038/s41439-026-00344-4","DOIUrl":"10.1038/s41439-026-00344-4","url":null,"abstract":"Large language models (LLMs) have recently been adopted to assist in the interpretation of human genomic variants. However, general-purpose LLMs can produce incorrect outputs (commonly termed 'hallucinations'), particularly on specialized queries, raising concerns about their reliability for variant interpretation. Here, to mitigate this risk, we developed ChatTogoVar, a retrieval-augmented generation system that queries TogoVar, a variant database that integrates information, such as allele frequency and clinical significance, and incorporates the retrieved results into prompts. We constructed a benchmark of 150 questions sampled from a predefined pool of 1500 template-variant combinations (50 templates × 30 variants). For large-scale assessment, we used the full 1500-question pool for automated LLM-based scoring. ChatTogoVar achieved the highest score for 135/150 questions, outperforming both a general-purpose LLM and an existing specialized system. Furthermore, automatic evaluation of all 1500 questions by an LLM confirmed the same trend. These results suggest that integrating a reliable variant database with an LLM can improve the accuracy of variant interpretation and that ChatTogoVar may serve as a practical tool to support genomic medicine and personalized healthcare.","PeriodicalId":36861,"journal":{"name":"Human Genome Variation","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646811","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

Clinical features of syndromic microphthalmia in two novel RARB variants. 两种新的RARB变异的综合征型小眼的临床特征。

IF 1.3

Human Genome Variation Pub Date : 2026-04-06 DOI: 10.1038/s41439-026-00345-3

Yoshito Koyanagi, Hazuki Morikawa-Anzai, Tomoyo Yoshida, Makiko Tominaga, Yuichi Abe, Rika Kosaki, Keiko Matsubara, Maki Fukami, Sachiko Nishina

引用次数: 0

MSX1 variant causes nonsyndromic tooth agenesis in a Japanese patient. MSX1变异导致日本患者的非综合征性牙齿发育。

IF 1.3

Human Genome Variation Pub Date : 2026-04-02 DOI: 10.1038/s41439-026-00343-5

Yasuto Sano, Michiyo Ando, Reiko Tokuyama-Toda, Akiko Ota, Junichiro Machida, Kazuhito Satomura, Mitsuo Goto, Yoshihito Tokita

引用次数: 0

Heterozygous frameshift KMT2A variant in a patient with Wiedemann-Steiner syndrome. Wiedemann-Steiner综合征患者的杂合移码KMT2A变异。

IF 1.3

Human Genome Variation Pub Date : 2026-03-17 DOI: 10.1038/s41439-026-00338-2

Sawako Hirai, Hiroshi Mitsubuchi, Shirou Matsumoto

引用次数: 0

Non-pterygium Escobar syndrome from compound-heterozygous CHRNG variants: genotype-phenotype insights. 复合杂合CHRNG变异引起的非翼状胬肉埃斯科瓦尔综合征：基因型-表型的见解。

IF 1.3

Human Genome Variation Pub Date : 2026-03-14 DOI: 10.1038/s41439-026-00340-8

Jun Kido, Hiroe Ueno, Yohei Misumi, Keishin Sugawara, Suzuran Saito, Eriko Koshimizu, Naomichi Matsumoto, Mitsuharu Ueda, Kimitoshi Nakamura

引用次数: 0

ZMYND11 p.Arg600Trp variant associated with a distinctive neurodevelopmental phenotype. 与一种特殊的神经发育表型相关的ZMYND11 p.Arg600Trp变异。

IF 1.3

Human Genome Variation Pub Date : 2026-03-12 DOI: 10.1038/s41439-026-00339-1

Hidetaka Yoshimatsu, Jun Kido, Takaaki Sawada, Keishin Sugawara, Yohei Misumi, Yukina Hayashi, Atsushi Fujita, Naomichi Matsumoto, Mitsuharu Ueda, Kimitoshi Nakamura

{"title":"ZMYND11 p.Arg600Trp variant associated with a distinctive neurodevelopmental phenotype.","authors":"Hidetaka Yoshimatsu, Jun Kido, Takaaki Sawada, Keishin Sugawara, Yohei Misumi, Yukina Hayashi, Atsushi Fujita, Naomichi Matsumoto, Mitsuharu Ueda, Kimitoshi Nakamura","doi":"10.1038/s41439-026-00339-1","DOIUrl":"10.1038/s41439-026-00339-1","url":null,"abstract":"Zinc finger MYND-type containing 11 (ZMYND11)-related neurodevelopmental disorder is an autosomal dominant condition caused by pathogenic variants in ZMYND11. Most previously reported patients harbor loss-of-function (LoF) variants, whereas missense variants are rare and their clinical and mechanistic characteristics remain insufficiently defined. Here we report a patient with a heterozygous ZMYND11 c.1798C>T, p.(Arg600Trp) variant identified through the Initiative on Rare and Undiagnosed Diseases program. Detailed clinical evaluation, developmental assessment and whole-exome sequencing were performed. In addition, a systematic review of previously published ZMYND11 cases was conducted to compare genotype-phenotype correlations between missense and LoF variants. The present patient showed global developmental delay, hypotonia, distinctive craniofacial features, microcephaly, short stature, cryptorchidism and right-sided inguinal hernia. Comparison with two previously reported individuals carrying the same c.1798C>T variant demonstrated consistent shared features, including microcephaly, broad nasal alae, short stature, cryptorchidism and nipple anomalies, findings that are not typically emphasized in LoF-associated cases. Aggregate analysis of reported 13 missense variants suggested higher frequencies of strabismus, hypotonia and severe intellectual disability compared with LoF variants, supporting the hypothesis that missense variants including c.1798C>T may define a partially distinct clinical subgroup. These findings expand the phenotypic spectrum associated with ZMYND11 missense variants and suggest variant-specific clinical patterns, particularly for c.1798C>T, which may reflect a mechanism different from simple haploinsufficiency.","PeriodicalId":36861,"journal":{"name":"Human Genome Variation","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13000240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445158","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 novel loss-of-function mutation in MCMDC2 is associated with male infertility. 一种新的MCMDC2功能缺失突变与男性不育有关。

IF 1.3

Human Genome Variation Pub Date : 2026-03-12 DOI: 10.1038/s41439-026-00342-6

Ori Cohen, Florence Abou, Netanel Waldenberg, Moran Gershoni, Sandra E Kleiman, Ruti Parvari, Shlomi Barak

引用次数: 0

Novel nonsense variant of KIF11 in a patient with MCLMR. MCLMR患者中KIF11的新无义变体。

IF 1.3

Human Genome Variation Pub Date : 2026-03-02 DOI: 10.1038/s41439-026-00341-7

Yuko Ozaki, Kyoko Yokoi, Yasuhisa Nakamura, Masanori Fujimoto, Risako Ishioka, Kozue Kasukabe, Takenori Kato, Shinji Saitoh

引用次数: 0

Population frequencies of thiopurine-related pharmacogenes in healthy individuals from Kosovo. 科索沃健康人群中硫嘌呤相关药物原基因的人群频率

IF 1.3

Human Genome Variation Pub Date : 2026-02-27 DOI: 10.1038/s41439-026-00337-3

Flaka Pasha, Dunja Urbančič, Gordana Gosheva, Bukurije Zhubi, Safete Maliqi Qormemeti, Shaip Krasniqi, Irena Mlinarič-Raščan

{"title":"Population frequencies of thiopurine-related pharmacogenes in healthy individuals from Kosovo.","authors":"Flaka Pasha, Dunja Urbančič, Gordana Gosheva, Bukurije Zhubi, Safete Maliqi Qormemeti, Shaip Krasniqi, Irena Mlinarič-Raščan","doi":"10.1038/s41439-026-00337-3","DOIUrl":"10.1038/s41439-026-00337-3","url":null,"abstract":"Personalized thiopurine therapy is among the most established examples of pharmacogenomics translated into clinical practice. Variants in TPMT (rs1800462, rs1800460, rs1142345) and NUDT15 (rs116855232) are recognized clinical predictors of thiopurine efficacy and toxicity. Additional variants in genes such as PACSIN2 (rs2413739), ITPA (rs1127354) and MTHFR (rs1801133 and rs1801131), also contribute to variability in drug response. Here we characterize the frequency of the pharmacogenetic variants involved in thiopurine metabolism in a healthy population of Kosovo. We genotyped 299 healthy blood donors for polymorphisms. Among TPMT variant alleles, TPMT*3A was observed at a frequency of 2.0%, and the TPMT*3C at 0.1%. Notably, the MTHFR 677T variant (rs1801133) was significantly more frequent in the Kosovo population (49.8%) compared with the global and European frequencies. The minor allele frequency of MTHFR rs1801131 was 27.4%. Minor allele frequencies for PACSIN2 rs2413739 and ITPA rs1127354 variants were 48.8% and 4.0%, respectively. Sequencing of NUDT15 revealed six variants, with rs116855232 present at frequency of 0.8%. These findings provide important insights into the pharmacogenomic profile of the Kosovo population and support the implementation of pre-emptive genotyping to improve the safety and efficacy of thiopurine therapy in the region.","PeriodicalId":36861,"journal":{"name":"Human Genome Variation","volume":"13 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147318263","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