Human Genome Variation最新文献

Functional evidence for SCN8A splice-donor variant c.4419+1 A > G causing loss of function. SCN8A剪接供体变异c.4419+1 A > G导致功能丧失的功能证据。

IF 1.3

Human Genome Variation Pub Date : 2026-06-29 DOI: 10.1038/s41439-026-00356-0

Takashi Shibata, Tomoyuki Akiyama, Takuma Harasaki, Sachiko Miyamoto, Hirotomo Saitsu, Toshiki Takenouchi

引用次数: 0

A novel truncating FBN1 variant in a family with Marfan syndrome. 马凡氏综合征家族中一种新的截断型FBN1变异。

IF 1.3

Human Genome Variation Pub Date : 2026-06-12 DOI: 10.1038/s41439-026-00355-1

Yuka Ito, Hiroshi Suzumura, Yuko Tanaka, George Imataka, Shujiro Hayashi, Yoshimasa Kawarai, Hiroko Susaka, Miyuki Muramatsu, Hiromi Yuasa, Wakana Soeda, Sakae Ito, Takahiko Kogai, Takahiro Yamada, Katsuhiko Naruse

引用次数: 0

Post-mortem diagnosis of CACT deficiency with a novel SLC25A20 variant. 一种新的SLC25A20变异的死后诊断CACT缺乏症。

IF 1.3

Human Genome Variation Pub Date : 2026-06-12 DOI: 10.1038/s41439-026-00354-2

Hiromi Nyuzuki, Aya Miura, Takuma Yamamoto, Akihide Koyama, Kazuhisa Funayama, Satoru Takami, Saori Fujita, Youko Kuriyama, Hisakazu Takatsuka, Hajime Nishio, Takeshi Ikeuchi

引用次数: 0

Integrated targeted whole-genome and RNA-sequencing analysis of an intronic GNE variant in GNE myopathy. GNE肌病中内含子基因变异的全基因组和rna测序分析。

IF 1.3

Human Genome Variation Pub Date : 2026-06-10 DOI: 10.1038/s41439-026-00352-4

Nozomi Toide, Ryo Iwase, Mitsugu Yanagidaira, Sumihito Togi, Hiroki Ura, Makiko Egawa, Eriko Takamine, Hiroya Kuwahara, Sonoko Misawa, Masayuki Yoshida, Yo Niida, Taro Ishiguro

{"title":"Integrated targeted whole-genome and RNA-sequencing analysis of an intronic GNE variant in GNE myopathy.","authors":"Nozomi Toide, Ryo Iwase, Mitsugu Yanagidaira, Sumihito Togi, Hiroki Ura, Makiko Egawa, Eriko Takamine, Hiroya Kuwahara, Sonoko Misawa, Masayuki Yoshida, Yo Niida, Taro Ishiguro","doi":"10.1038/s41439-026-00352-4","DOIUrl":"10.1038/s41439-026-00352-4","url":null,"abstract":"GNE myopathy is a rare autosomal recessive myopathy caused by biallelic pathogenic variants in GNE, which encodes an essential enzyme for sialic acid biosynthesis. Most variants are located in exonic regions, whereas significance of intronic variants remains unclear, leaving many suspected cases genetically unresolved. We aimed to assess the pathogenicity of intronic GNE variants using targeted whole-genome and RNA sequencing. We performed combined long amplicon sequencing in two siblings with GNE myopathy. DNA and RNA were extracted from muscle biopsy specimens and peripheral blood mononuclear cells. Variants were validated using Sanger sequencing. Splicing effects were predicted using SpliceAI and SpliceRover and validated by RNA sequencing. Muscle sialylation was assessed using peanut agglutinin lectin staining. An uncharacterized intronic variant, NC_000009.12(NM_001128227): c.1163+5G>T, was identified in trans with a known missense variant (NM_001128227): c.1807C>G, p.V603L. RNA sequencing demonstrated aberrant splicing caused by intronic mutation, leading to a non-productive transcript in muscle and blood cells. Reduced sialic acid biosynthesis further supported the pathogenicity of the intronic mutation. These findings demonstrate that combined long amplicon sequencing can elucidate the genetic basis of GNE myopathy undetectable by exome sequencing. This approach provides a clinically applicable, less invasive diagnostic strategy and expands the spectrum of pathogenic GNE variants.","PeriodicalId":36861,"journal":{"name":"Human Genome Variation","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212725","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

Cleidocranial dysplasia caused by a novel de novo RUNX2 splice-site variant. 由一种新的RUNX2剪接位点变异引起的锁骨颅内发育不良。

IF 1.3

Human Genome Variation Pub Date : 2026-06-04 DOI: 10.1038/s41439-026-00353-3

Hitoshi Kashiki, Jun Kido, Yohei Misumi, Keishin Sugawara, Naomi Tsuchida, Naomichi Matsumoto, Mitsuharu Ueda, Kimitoshi Nakamura

引用次数: 0

Carney complex with PRKAR1A variant and breast/fibrolamellar carcinomas. Carney复合物与PRKAR1A变异和乳腺/纤维板层癌。

IF 1.3

Human Genome Variation Pub Date : 2026-05-28 DOI: 10.1038/s41439-026-00351-5

Abílio Alonso Colares Perez, Laura Pinheiro Correia, Régis Ponte Conrado, Vinícius Nascimento Malheiro, Carlos Gustavo Hirth, Diane Isabelle Magno Cavalcante, Gustavo Rêgo Coelho, Ana Rosa Pinto Quidute, Danielle Calheiros Campelo Maia

{"title":"Carney complex with PRKAR1A variant and breast/fibrolamellar carcinomas.","authors":"Abílio Alonso Colares Perez, Laura Pinheiro Correia, Régis Ponte Conrado, Vinícius Nascimento Malheiro, Carlos Gustavo Hirth, Diane Isabelle Magno Cavalcante, Gustavo Rêgo Coelho, Ana Rosa Pinto Quidute, Danielle Calheiros Campelo Maia","doi":"10.1038/s41439-026-00351-5","DOIUrl":"10.1038/s41439-026-00351-5","url":null,"abstract":"Carney complex is a rare multiple neoplasia syndrome caused primarily by inactivating variants in the PRKAR1A gene, which encodes the regulatory subunit type I alpha of protein kinase A. Although classically associated with myxomas, lentigines, and endocrine tumors, the full tumor spectrum related to PRKAR1A loss of function is not completely defined. Here, we report a patient with a molecularly confirmed diagnosis of Carney complex carrying a de novo PRKAR1A (NM_002734.5):c.348+1G>A splice-site variant. In addition to typical manifestations, the patient developed two uncommon malignancies: invasive breast carcinoma (luminal B-like) at a young age and fibrolamellar hepatocellular carcinoma lacking the DNAJB1-PRKACA fusion typically found in sporadic cases. The coexistence of these two rare tumors in a single carrier of a pathogenic PRKAR1A variant expands the phenotypic variability associated with this condition and supports the possibility that PRKAR1A loss contributes to oncogenesis beyond the classical endocrine and mesenchymal tissues. This Data Report provides clinically relevant documentation of an unusual tumor presentation associated with a pathogenic PRKAR1A variant and underscores the importance of ongoing clinical surveillance in affected individuals.","PeriodicalId":36861,"journal":{"name":"Human Genome Variation","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057394","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, genetics and in silico analysis of a novel BSCL2 variant in a patient with CGL2 from Iranian Azeri Turkish ethnic group: expanding the genotypic spectrum through a comparative review. 来自伊朗阿塞拜疆土耳其族裔的CGL2患者的新型BSCL2变异的临床、遗传学和计算机分析：通过比较回顾扩大基因型谱。

IF 1.3

Human Genome Variation Pub Date : 2026-05-04 DOI: 10.1038/s41439-026-00350-6

Hadi Bazmi, Neda Jabbarpour, Asma Alizadeh Asghari, Morteza Bonaydi, Akram Motamedi, Mohammad Barzegar

引用次数: 0

Duplication of 4-bp in SACS leads to autosomal recessive spastic ataxia of Charlevoix-Saguenay type in two Pakistani patients. SACS中4-bp的重复导致两名巴基斯坦患者的常染色体隐性查理-萨格奈型痉挛性共济失调。

IF 1.3

Human Genome Variation Pub Date : 2026-04-28 DOI: 10.1038/s41439-026-00349-z

Saba Bibi, Asad Munir, Fawad Ali, Helen Nabiryo Frederiksen, Sabawoon Shah, Abdur Rashid, Sergey Oreshkov, Shahab Uddin, Hamid Ur Rahman, Shumaila Noreen, Mukhtar Ullah, Muhammad Ansar, Atta Ur Rehman

引用次数: 0

Pontocerebellar hypoplasia type 9 with a novel combination of compound heterozygous variants in AMPD2. 9型桥小脑发育不全与AMPD2复合杂合变异的新组合。

IF 1.3

Human Genome Variation Pub Date : 2026-04-23 DOI: 10.1038/s41439-026-00348-0

Shuhei Dohi, Junko Hotta, Kosuke Ito, Tomoyo Yamashita, Chie Ono, Satoru Sakuma, Kazuyuki Komatsu, Ken Inoue, Hirotomo Saitsu, Takashi Hamazaki, Toshiyuki Seto

引用次数: 0

Long-read RNA sequencing reveals extensive transcript isoform changes in a patient with IFAP syndrome with a recurrent intronic MBTPS2 variant. 长读RNA测序揭示了伴有复发性内含子MBTPS2变异的IFAP综合征患者广泛的转录异构体变化。

IF 1.3

Human Genome Variation Pub Date : 2026-04-14 DOI: 10.1038/s41439-026-00347-1

Toshihiko Iwaki, Yosuke Nishio, Sachiyo Takagi, Keiichiro Fujii, Masanori Fujimoto, Emi Sato, Yuji Nakamura, Daisuke Ieda, Yutaka Negishi, Ayako Hattori, Tomoo Ogi, Shinji Saitoh

{"title":"Long-read RNA sequencing reveals extensive transcript isoform changes in a patient with IFAP syndrome with a recurrent intronic MBTPS2 variant.","authors":"Toshihiko Iwaki, Yosuke Nishio, Sachiyo Takagi, Keiichiro Fujii, Masanori Fujimoto, Emi Sato, Yuji Nakamura, Daisuke Ieda, Yutaka Negishi, Ayako Hattori, Tomoo Ogi, Shinji Saitoh","doi":"10.1038/s41439-026-00347-1","DOIUrl":"10.1038/s41439-026-00347-1","url":null,"abstract":"Hemizygous pathogenic variants in MBTPS2 located at Xp22.12 cause IFAP syndrome, which is characterized by the triad of ichthyosis, alopecia and photophobia. Here we identified a hemizygous intronic variant in MBTPS2 (NM_015884: c.970+5G>A) in a patient with alopecia, follicular keratinization, developmental delay and epilepsy which were compatible with IFAP syndrome. The variant has been reported to cause skipping of 20 bases in exon 7, leading to the premature termination codon. To further investigate the consequence of the variant, we performed long-read RNA sequencing using RNA extracted from fibroblasts cultured from the patient's skin. Long-read RNA sequencing revealed skipping of exons 6 and 7, in addition to the previously reported 20-base skipping in exon 7. Furthermore, the expression of normal transcripts, as observed in healthy skin, was markedly reduced. Long-read RNA sequencing is a powerful tool for simultaneously identifying diverse transcript isoforms, making it highly valuable for elucidating the effects of splice-altering variants.","PeriodicalId":36861,"journal":{"name":"Human Genome Variation","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692319","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