Human Genome Variation最新文献_第2页

Homozygous 6-bp deletion of IGFALS in a prepubertal boy with short stature. 一名青春期前身材矮小男孩的 IGFALS 基因出现 6-bp 缺失。

IF 1

Human Genome Variation Pub Date : 2024-07-26 DOI: 10.1038/s41439-024-00285-w

Hibiki Doi, Ikuko Kageyama, Yuko Katoh-Fukui, Atsushi Hattori, Maki Fukami, Naoto Shimura

引用次数: 0

TACSTD2 in gelatinous drop-like corneal dystrophy: variant functional analysis and expression in the cornea after limbal stem cell transplantation. 胶样角膜营养不良症中的TACSTD2：变体功能分析和角膜缘干细胞移植后的表达。

IF 1

Human Genome Variation Pub Date : 2024-07-16 DOI: 10.1038/s41439-024-00284-x

Liubov O Skorodumova, Ekaterina N Grafskaia, Daria D Kharlampieva, Dmitry I Maltsev, Tatiana V Petrova, Alexandra V Kanygina, Elena V Fedoseeva, Pavel V Makarov, Boris E Malyugin

{"title":"TACSTD2 in gelatinous drop-like corneal dystrophy: variant functional analysis and expression in the cornea after limbal stem cell transplantation.","authors":"Liubov O Skorodumova, Ekaterina N Grafskaia, Daria D Kharlampieva, Dmitry I Maltsev, Tatiana V Petrova, Alexandra V Kanygina, Elena V Fedoseeva, Pavel V Makarov, Boris E Malyugin","doi":"10.1038/s41439-024-00284-x","DOIUrl":"10.1038/s41439-024-00284-x","url":null,"abstract":"Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive eye disease. GDLD is characterized by the loss of barrier function in corneal epithelial cells (CECs) and amyloid deposition due to pathogenic variants in the TACSTD2 gene. Limbal stem cell transplantation (LSCT) has been suggested as an effective therapeutic alternative for patients with GDLD. However, despite LSCT, amyloid deposition recurs in some patients. The pathogenesis of recurrence is poorly studied. We present the case of a patient with GDLD. Genetic analysis revealed a homozygous deletion, NM_002353.3:c.653del, in the TACSTD2 gene. Functional analysis in a cell model system revealed the loss of the transmembrane domain and subcellular protein mislocalization. The patient with GDLD underwent direct allogeneic LSCT with epithelial debridement followed by deep anterior lamellar keratoplasty 10 months later due to amyloid deposition and deterioration of vision. Taken together, the results of transcriptome analysis and immunofluorescence staining of post-LSCT corneal sample with amyloid deposits obtained during keratoplasty demonstrated complete restoration of wild-type TACSTD2 expression, indicating that donor CECs replaced host CECs. Our study provides experimental evidence that amyloid deposition can recur after LSCT despite complete restoration of wild-type TACSTD2 expression.","PeriodicalId":36861,"journal":{"name":"Human Genome Variation","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627951","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

Identifying unstable CNG repeat loci in the human genome: a heuristic approach and implications for neurological disorders. 识别人类基因组中不稳定的 CNG 重复位点：启发式方法及其对神经系统疾病的影响。

IF 1.5

Human Genome Variation Pub Date : 2024-06-13 DOI: 10.1038/s41439-024-00281-0

Varun Suroliya, Bharathram Uppili, Manish Kumar, Vineet Jha, Achal K Srivastava, Mohammed Faruq

{"title":"Identifying unstable CNG repeat loci in the human genome: a heuristic approach and implications for neurological disorders.","authors":"Varun Suroliya, Bharathram Uppili, Manish Kumar, Vineet Jha, Achal K Srivastava, Mohammed Faruq","doi":"10.1038/s41439-024-00281-0","DOIUrl":"10.1038/s41439-024-00281-0","url":null,"abstract":"Tandem nucleotide repeat (TNR) expansions, particularly the CNG nucleotide configuration, are associated with a variety of neurodegenerative disorders. In this study, we aimed to identify novel unstable CNG repeat loci associated with the neurogenetic disorder spinocerebellar ataxia (SCA). Using a computational approach, 15,069 CNG repeat loci in the coding and noncoding regions of the human genome were identified. Based on the feature selection criteria (repeat length >10 and functional location of repeats), we selected 52 repeats for further analysis and evaluated the repeat length variability in 100 control subjects. A subset of 19 CNG loci observed to be highly variable in control subjects was selected for subsequent analysis in 100 individuals with SCA. The genes with these highly variable repeats also exhibited higher gene expression levels in the brain according to the tissue expression dataset (GTEx). No pathogenic expansion events were identified in patient samples, which is a limitation given the size of the patient group examined; however, these loci contain potential risk alleles for expandability. Recent studies have implicated GLS, RAI1, GIPC1, MED15, EP400, MEF2A, and CNKSR2 in neurological diseases, with GLS, GIPC1, MED15, RAI1, and MEF2A sharing the same repeat loci reported in this study. This finding validates the approach of evaluating repeat loci in different populations and their possible implications for human pathologies.","PeriodicalId":36861,"journal":{"name":"Human Genome Variation","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318478","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

Allele frequency of pathogenic variants causing acid sphingomyelinase deficiency and Gaucher disease in the general Japanese population. 日本普通人群中导致酸性鞘磷脂酶缺乏症和戈谢病的致病变体的等位基因频率。

IF 1.5

Human Genome Variation Pub Date : 2024-06-12 DOI: 10.1038/s41439-024-00282-z

Shuhei Sako, Kimihiko Oishi, Hiroyuki Ida, Eri Imagawa

{"title":"Allele frequency of pathogenic variants causing acid sphingomyelinase deficiency and Gaucher disease in the general Japanese population.","authors":"Shuhei Sako, Kimihiko Oishi, Hiroyuki Ida, Eri Imagawa","doi":"10.1038/s41439-024-00282-z","DOIUrl":"10.1038/s41439-024-00282-z","url":null,"abstract":"Acid sphingomyelinase deficiency (ASMD) and Gaucher disease (GD) are lysosomal storage disorders associated with hepatosplenomegaly and thrombocytopenia. The incidences of ASMD and GD are known to be particularly high in the Ashkenazi Jewish population. Conversely, the number of reported patients with these diseases has been limited in Asian countries, including Japan. Here, we reviewed the allele frequencies of pathogenic variants causing ASMD and GD in the Japanese population and populations with various ancestry backgrounds using the Japanese Multi-Omics Reference Panel 54KJPN and the Genome Aggregation Database v4.0.0. The estimated carrier frequencies of ASMD- and GD-related variants were 1/180 and 1/154 in Japanese individuals, equivalent to disease occurrence frequencies of 1/128,191 and 1/94,791 individuals, respectively. These frequencies are much higher than previously expected. Our data also suggest that there are more patients with a milder form of ASMD and nonspecific clinical findings who have not yet been diagnosed.","PeriodicalId":36861,"journal":{"name":"Human Genome Variation","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311849","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

Investigating mobile element variations by statistical genetics. 通过统计遗传学研究流动元素的变异。

IF 1.5

Human Genome Variation Pub Date : 2024-05-30 DOI: 10.1038/s41439-024-00280-1

Shohei Kojima

{"title":"Investigating mobile element variations by statistical genetics.","authors":"Shohei Kojima","doi":"10.1038/s41439-024-00280-1","DOIUrl":"10.1038/s41439-024-00280-1","url":null,"abstract":"The integration of structural variations (SVs) in statistical genetics provides an opportunity to understand the genetic factors influencing complex human traits and disease. Recent advances in long-read technology and variant calling methods for short reads have improved the accurate discovery and genotyping of SVs, enabling their use in expression quantitative trait loci (eQTL) analysis and genome-wide association studies (GWAS). Mobile elements are DNA sequences that insert themselves into various genome locations. Insertional polymorphisms of mobile elements between humans, called mobile element variations (MEVs), contribute to approximately 25% of human SVs. We recently developed a variant caller that can accurately identify and genotype MEVs from biobank-scale short-read whole-genome sequencing (WGS) datasets and integrate them into statistical genetics. The use of MEVs in eQTL analysis and GWAS has a minimal impact on the discovery of genome loci associated with gene expression and disease; most disease-associated haplotypes can be identified by single nucleotide variations (SNVs). On the other hand, it helps make hypotheses about causal variants or effector variants. Focusing on MEVs, we identified multiple MEVs that contribute to differential gene expression and one of them is a potential cause of skin disease, emphasizing the importance of the integration of MEVs in medical genetics. Here, I will provide an overview of MEVs, MEV calling from WGS, and the integration of MEVs in statistical genetics. Finally, I will discuss the unanswered questions about MEVs, such as rare variants.","PeriodicalId":36861,"journal":{"name":"Human Genome Variation","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180068","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

Characteristic craniofacial defects associated with a novel USP9X truncation mutation. 与新型 USP9X 截断突变相关的特征性颅面缺陷。

IF 1.5

Human Genome Variation Pub Date : 2024-05-16 DOI: 10.1038/s41439-024-00277-w

Namiki Nagata, Hiroshi Kurosaka, Kotaro Higashi, Masaya Yamaguchi, Sayuri Yamamoto, Toshihiro Inubushi, Miho Nagata, Yasuki Ishihara, Ayumi Yonei, Yohei Miyashita, Yoshihiro Asano, Norio Sakai, Yasushi Sakata, Shigetada Kawabata, Takashi Yamashiro

引用次数: 0

NF1 with 47,XYY mosaicism diagnosed by mandibular neurofibromas 通过下颌神经纤维瘤诊断出与 47,XYY 嵌合的 NF1

IF 1.5

Human Genome Variation Pub Date : 2024-05-16 DOI: 10.1038/s41439-024-00279-8

Erina Tonouchi, Kei-ichi Morita, Y. Harazono, Kyoko Hoshino, Tetsuya Yoda

引用次数: 0

NF1 with 47,XYY mosaicism diagnosed by mandibular neurofibromas. 通过下颌神经纤维瘤诊断出 NF1 与 47,XYY 嵌合。

IF 1.5

Human Genome Variation Pub Date : 2024-05-16 DOI: 10.1038/s41439-024-00279-8

Erina Tonouchi, Kei-Ichi Morita, Yosuke Harazono, Kyoko Hoshino, Tetsuya Yoda

引用次数: 0

Characteristic craniofacial defects associated with a novel USP9X truncation mutation 与新型 USP9X 截断突变相关的特征性颅面缺陷

IF 1.5

Human Genome Variation Pub Date : 2024-05-16 DOI: 10.1038/s41439-024-00277-w

Namiki Nagata, H. Kurosaka, Kotaro Higashi, Masaya Yamaguchi, Sayuri Yamamoto, Toshihiro Inubushi, Miho Nagata, Yasuki Ishihara, Ayumi Yonei, Yohei Miyashita, Yoshihiro Asano, Norio Sakai, Y. Sakata, Shigetada Kawabata, T. Yamashiro

引用次数: 0

Xq22 deletion involving TCEAL1 in a female patient with early-onset neurological disease trait. 一名女性早发性神经系统疾病患者体内涉及 TCEAL1 的 Xq22 缺失。

IF 1.5

Human Genome Variation Pub Date : 2024-05-15 DOI: 10.1038/s41439-024-00278-9

Keiko Shimojima Yamamoto, Yusuke Itagaki, Kazuki Tanaka, Nobuhiko Okamoto, Toshiyuki Yamamoto

引用次数: 0