Journal of Human Genetics最新文献

Hyaluronidase 2 deficiency due to novel compound heterozygous variants in HYAL2: a case report of siblings with HYAL2 deficiency showing different clinical severity and literature review. HYAL2中新型复合杂合变异体引起的透明质酸酶2缺陷：临床严重程度不同的兄弟姐妹HYAL2缺陷病例报告及文献复习

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2025-06-01 Epub Date: 2025-03-31 DOI: 10.1038/s10038-025-01333-1

Ryuta Orimoto, Eriko Adachi, Maki Gau, Yoko Saito, Haruki Yamano, Hisae Nakatani, Shizuka Kirino, Kengo Moriyama, Yohei Yamaguchi, Tomoko Mizuno, Taku Ishii, Masayuki Yoshida, Kenichi Kashimada, Kei Takasawa

{"title":"Hyaluronidase 2 deficiency due to novel compound heterozygous variants in HYAL2: a case report of siblings with HYAL2 deficiency showing different clinical severity and literature review.","authors":"Ryuta Orimoto, Eriko Adachi, Maki Gau, Yoko Saito, Haruki Yamano, Hisae Nakatani, Shizuka Kirino, Kengo Moriyama, Yohei Yamaguchi, Tomoko Mizuno, Taku Ishii, Masayuki Yoshida, Kenichi Kashimada, Kei Takasawa","doi":"10.1038/s10038-025-01333-1","DOIUrl":"10.1038/s10038-025-01333-1","url":null,"abstract":"This study reports the first Asian case of syndromic cleft lip and palate resembling CHARGE-like syndrome, caused by novel compound heterozygous variants of the HYAL2 gene. Hyaluronidase-2 (HYAL2) plays a critical role in hyaluronic acid degradation and tissue remodelling. A 2-year-old Japanese boy presented with growth deficiency, congenital heart disease, craniofacial dysmorphism, micropenis, and developmental delays-features that overlapped with those of CHARGE syndrome. Genetic analysis identified two rare HYAL2 missense variants (c.1133G>A, p.Arg378His; c.1271A>G, p.His424Arg), classified as \"likely pathogenic\" based on ACMG/AMP criteria. This case highlights the importance of considering HYAL2 deficiency in the syndromic presentation of cleft lip and palate with congenital heart disease, particularly in the absence of CHD7 abnormalities. This study also emphasizes potential primary testicular dysfunction in male patients with HYAL2 deficiency and underscores the need for further research to clarify genotype-phenotype correlations and pathology.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":"321-324"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Profiling of runs of homozygosity from whole-genome sequence data in Japanese biobank. 日本生物库全基因组序列数据的纯合性分析。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2025-06-01 Epub Date: 2025-04-03 DOI: 10.1038/s10038-025-01331-3

Aye Ko Ko Minn, Motomichi Matsuzaki, Akira Narita, Takamitsu Funayama, Yurii Kotsar, Satoshi Makino, Jun Takayama, Shinichi Kuriyama, Gen Tamiya

{"title":"Profiling of runs of homozygosity from whole-genome sequence data in Japanese biobank.","authors":"Aye Ko Ko Minn, Motomichi Matsuzaki, Akira Narita, Takamitsu Funayama, Yurii Kotsar, Satoshi Makino, Jun Takayama, Shinichi Kuriyama, Gen Tamiya","doi":"10.1038/s10038-025-01331-3","DOIUrl":"10.1038/s10038-025-01331-3","url":null,"abstract":"Runs of homozygosity (ROHs) are widely observed across the genomes of various species and have been reported to be associated with many traits and common diseases, as well as rare recessive diseases, in human populations. Although single nucleotide polymorphism (SNP) array data have been used in previous studies on ROHs, recent advances in whole-genome sequencing (WGS) technologies and the development of nationwide cohorts/biobanks are making high-density genomic data increasingly available, and it is consequently becoming more feasible to detect ROHs at higher resolution. In the study, we searched for ROHs in two high-coverage WGS datasets from 3552 Japanese individuals and 192 three-generation families (consisting of 1120 family members) in prospective genomic cohorts. The results showed that a considerable number of ROHs, especially short ones that may have remained undetected in conventionally used SNP-array data, can be detected in the WGS data. By filtering out sequencing errors and leveraging pedigree information, longer ROHs are more likely to be detected in WGS data than in SNP-array data. Additionally, we identified gene families within ROH islands that are associated with enriched pathways related to sensory perception of taste and odors, suggesting potential signatures of selection in these key genomic regions.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":"287-296"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heterogeneity of the Southeast Belarusian mitochondrial gene pool. 白俄罗斯东南部线粒体基因库的异质性。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2025-06-01 Epub Date: 2025-04-07 DOI: 10.1038/s10038-025-01337-x

Boris Malyarchuk, Galina Denisova, Andrey Litvinov

{"title":"Heterogeneity of the Southeast Belarusian mitochondrial gene pool.","authors":"Boris Malyarchuk, Galina Denisova, Andrey Litvinov","doi":"10.1038/s10038-025-01337-x","DOIUrl":"10.1038/s10038-025-01337-x","url":null,"abstract":"The study of mitochondrial DNA (mtDNA) variability at the level of whole mitogenomes has significant implications for the fields of human evolution and population genetics. In this paper, we present the results of a study of the complete mtDNA variability in Belarusians from the southeastern part of the Republic of Belarus. It was found that Southeast Belarusians are characterized by a high diversity of mitochondrial genomes. The analysis of genetic distances between European populations showed significant differences between the studied Belarusian sample from the bulk of East European populations, including Slavic ethnic groups. The results of the phylogeographic analysis indicated the presence of the West Asian component (12.6%) in the Belarusian mitochondrial gene pool, which can account for the observed genetic differences between Belarusians and other Eastern Slavs (Russians and Ukrainians). The East Asian component of the mitochondrial gene pool of the studied group of Belarusians is represented by haplogroup C5c1a (2.3%). The results of the phylogeographic analysis indicated that this mtDNA subclade is predominantly present in the gene pools of Slavic peoples, including Poles, Belarusians, Ukrainians, and Russians. The evolutionary age of haplogroup C5c1a is ~4000 years and, consequently, the appearance of C5c1-haplotypes in the eastern regions of Europe may be linked to the migrations of the Caspian steppe populations to the west during the Bronze Age.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":"313-320"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Significance of noninvasive prenatal testing using massively parallel sequencing in women with twin or vanishing twin pregnancies. 大规模平行测序对双胎或消失双胎妊娠妇女进行无创产前检测的意义。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2025-06-01 Epub Date: 2025-03-28 DOI: 10.1038/s10038-025-01332-2

Eri Takeda, Nobuhiro Suzumori, Osamu Samura, Kiyonori Miura, Yoshimasa Kamei, Hideaki Sawai, Takahiro Yamada, Kiyotake Ichizuka, Reina Komatsu, Seiji Wada, Yukiko Katagiri, Hiroko Morisaki, Setsuko Nakayama, Haruka Hamanoue, Jun Murotsuki, Kazuya Mimura, Yuko Matsubara, Kazuhisa Maeda, Akinori Ida, Mika Ito, Hiromi Hayakawa, Arisa Fujiwara, Nahoko Shirato, Tatsuko Ishii, Haruhiko Sago, Akihiko Sekizawa

{"title":"Significance of noninvasive prenatal testing using massively parallel sequencing in women with twin or vanishing twin pregnancies.","authors":"Eri Takeda, Nobuhiro Suzumori, Osamu Samura, Kiyonori Miura, Yoshimasa Kamei, Hideaki Sawai, Takahiro Yamada, Kiyotake Ichizuka, Reina Komatsu, Seiji Wada, Yukiko Katagiri, Hiroko Morisaki, Setsuko Nakayama, Haruka Hamanoue, Jun Murotsuki, Kazuya Mimura, Yuko Matsubara, Kazuhisa Maeda, Akinori Ida, Mika Ito, Hiromi Hayakawa, Arisa Fujiwara, Nahoko Shirato, Tatsuko Ishii, Haruhiko Sago, Akihiko Sekizawa","doi":"10.1038/s10038-025-01332-2","DOIUrl":"10.1038/s10038-025-01332-2","url":null,"abstract":"Noninvasive prenatal testing diagnoses fetal aneuploidies in singleton pregnancies with trisomy 21, 18, or 13 accurately. However, clinical data on noninvasive prenatal testing in women with twin or vanishing twin pregnancies are limited. We report on the accuracy and prenatal and neonatal outcomes of noninvasive prenatal testing in twin and vanishing twin pregnancies. This retrospective study was conducted at 22 facilities belonging to the Noninvasive Prenatal Testing Consortium, part of a nationwide project in Japan, visited by women with twin or vanishing twin pregnancies between January 2015 and March 2022. This study investigated the accuracy and perinatal and neonatal outcomes of noninvasive prenatal testing using massively parallel sequencing in twin or vanishing twin pregnancies. Of 1013 women with twin pregnancies, 986 (97.3%) had negative; 13 (1.3%), positive; and 14 (1.4%), non-reportable noninvasive prenatal testing results. Of 225 women with vanishing twins, 203 (90.2%) had negative; 11 (4.9%), positive; and 11 (4.9%), non-reportable results. Among 1693 fetuses (77.3%) excluding 497 unknowns were available for follow-up, 1476 were from twin pregnancies, and 134 were from vanishing twin pregnancies, totaling 1610 babies has born. No false negatives were observed in the cases followed. These results indicate that noninvasive prenatal testing is useful for vanishing twin pregnancies and provide reassurance for pregnant women with twins and vanishing twins.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":"297-305"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","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 case of autosomal-dominant cutis laxa caused by a de novo likely pathogenic variant in ALDH18A1: case report and literature review. 由ALDH18A1可能的新致病变异引起的常染色体显性皮肤松弛症一例：病例报告及文献复习。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2025-06-01 Epub Date: 2025-03-31 DOI: 10.1038/s10038-025-01334-0

Firoz Ahmad, Pradnya Gadgil, Noopur Navandar, Sapna Sandal, Mukesh Kumar, Amisha Shah, Meenu Angi, Pooja Chaudhary, Ekta Jajodia, Toral Vaishnani, Anindyajit Banerjee, Spandan Chaudhary, Neeraj Arora

{"title":"A novel case of autosomal-dominant cutis laxa caused by a de novo likely pathogenic variant in ALDH18A1: case report and literature review.","authors":"Firoz Ahmad, Pradnya Gadgil, Noopur Navandar, Sapna Sandal, Mukesh Kumar, Amisha Shah, Meenu Angi, Pooja Chaudhary, Ekta Jajodia, Toral Vaishnani, Anindyajit Banerjee, Spandan Chaudhary, Neeraj Arora","doi":"10.1038/s10038-025-01334-0","DOIUrl":"10.1038/s10038-025-01334-0","url":null,"abstract":"Cutis laxa is a highly heterogeneous connective tissue disorder characterized by progressively loose skin, often accompanied by systemic involvement. Autosomal dominant cutis laxa (ADCL) has been linked to variants in several genes, including ALDH18A1, which encodes Δ1-pyrroline-5-carboxylate synthetase, a key enzyme in proline and collagen metabolism. We report a novel case of ADCL in a 1.6-year-old patient presenting with growth delay, hypotonia, joint laxity, lax skin, cataract, dysmorphic features, microcephaly, cranial vessel tortuosity, hip dislocation, and psychomotor retardation. Whole-exome sequencing revealed a de novo heterozygous c.400 T > C (p.Ser134Pro) substitution in the ALDH18A1 gene. This variant has not been previously reported, and it is the first report of an individual with ALDH18A1-ADCL due to a substitution at a highly conserved residue, p.Ser134 of the P5CS protein. Our findings expand the mutational spectrum of ALDH18A1-related ADCL and highlight the importance of genetic testing in diagnosing rare disorders.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":"325-329"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mosaic deletions detected by genome sequencing in two families. 基因组测序检测两个家族的嵌合缺失。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2025-06-01 Epub Date: 2025-04-09 DOI: 10.1038/s10038-025-01336-y

Naomi Tsuchida, Yuri Uchiyama, Kohei Hamanaka, Nobuhiko Okamoto, Ayataka Fujimoto, Hideo Enoki, Eriko Koshimizu, Atsushi Fujita, Kazuharu Misawa, Satoko Miyatake, Takeshi Mizuguchi, Naomichi Matsumoto

引用次数: 0

Reclassification of variants of uncertain significance in neonatal genetic diseases: implications from a clinician's perspective. 新生儿遗传疾病中不确定意义变异的重新分类：从临床医生角度的意义。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2025-05-12 DOI: 10.1038/s10038-025-01348-8

Xiaojiao Wu, Jiancheng Jiao, Weicong Pu, Xiaotong Yan, Yaofang Xia, Weiwei Guo, Li Ma, Yanyan Cao

{"title":"Reclassification of variants of uncertain significance in neonatal genetic diseases: implications from a clinician's perspective.","authors":"Xiaojiao Wu, Jiancheng Jiao, Weicong Pu, Xiaotong Yan, Yaofang Xia, Weiwei Guo, Li Ma, Yanyan Cao","doi":"10.1038/s10038-025-01348-8","DOIUrl":"https://doi.org/10.1038/s10038-025-01348-8","url":null,"abstract":"Although whole-exome sequencing (WES) is now widely used to diagnose neonatal genetic diseases, the genetic causes in over half of the cases remain unresolved, primarily due to variants of uncertain significance (VUS). Therefore, reclassifying VUS may be an effective strategy to improve WES's diagnostic yield. However, not all reclassification approaches are suitable for clinicians. Patients in the neonatal unit of Hebei Provincial Children's Hospital who underwent WES for suspected genetic diseases and demonstrated VUS were re-evaluated from January 2019 to December 2023 using user-friendly methods. A total of 676 individuals were tested, with 101 phenotype-associated VUS identified in 82 patients. Thirty (29.7%) VUS classifications were changed: 24 were upgraded to likely pathogenic or pathogenic, and 6 were downgraded to likely benign. VUS reclassification clarified the molecular diagnosis in 19 cases, increasing the WES diagnostic rate from 30.2% to 33.0%. Computational prediction contributed the most to reclassification, whereas clinical phenotype-related evidence was also particularly significant in upgrading variants. Moreover, phenotype-associated VUS with a score of ≥3 points are more likely to be classified as likely pathogenic or pathogenic, thus requiring more attention. This study provides a practical reference for clinicians in managing VUS reclassification.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The usefulness of comprehensive genome profiling test in screening of Lynch syndrome independent of the conventional clinical screening or microsatellite instability tests. 综合基因组谱检测在Lynch综合征筛查中的作用独立于传统临床筛查或微卫星不稳定性试验。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2025-05-08 DOI: 10.1038/s10038-025-01345-x

Mizuki Yamaguchi, Shintaro Akabane, Hiroaki Niitsu, Hikaru Nakahara, Asuka Toshida, Tetsuya Mochizuki, Takuya Yano, Yoshihiro Saeki, Hiroshi Okuda, Manabu Shimomura, Kazuhiro Sentani, Kiwamu Akagi, Hideki Ohdan, Takao Hinoi

{"title":"The usefulness of comprehensive genome profiling test in screening of Lynch syndrome independent of the conventional clinical screening or microsatellite instability tests.","authors":"Mizuki Yamaguchi, Shintaro Akabane, Hiroaki Niitsu, Hikaru Nakahara, Asuka Toshida, Tetsuya Mochizuki, Takuya Yano, Yoshihiro Saeki, Hiroshi Okuda, Manabu Shimomura, Kazuhiro Sentani, Kiwamu Akagi, Hideki Ohdan, Takao Hinoi","doi":"10.1038/s10038-025-01345-x","DOIUrl":"https://doi.org/10.1038/s10038-025-01345-x","url":null,"abstract":"Lynch syndrome (LS) is a hereditary cancer predisposition syndrome caused by germline pathogenic variants of DNA mismatch repair (MMR) genes. To diagnose LS, the microsatellite instability (MSI) test or immunohistochemistry of MMR enzymes is used as a conventional clinical screening method for all patients with colorectal and endometrial cancers. Recently, patients with advanced-stage cancers have undergone comprehensive genomic profiling (CGP), which is useful not only for the detection of molecularly targeted personalized therapies, but also for the screening of hereditary cancer syndromes by determining presumed germline pathogenic variants (PGPVs). Between January 2020 and April 2024, 1583 patients underwent CGP at our institute. PGPVs in MMR genes were detected in 19 patients. Although one patient died prior to the disclosure of the results and eight patients declined confirmatory genetic testing, the remaining ten patients underwent confirmatory genetic tests, of whom six were found to have a hereditary origin. Two additional patients were diagnosed with LS using tumor-normal paired CGP. Eventually, a total of eight patients were diagnosed with LS. Herein, we describe two patients with microsatellite-stable cancer who could not be diagnosed using conventional clinical screening or MSI testing. Furthermore, we showed that pathogenic variants of MMR genes do not always correlate with high MSI prediction scores in several cancer types in The Cancer Genome Atlas (TCGA) dataset analysis. These findings highlight the usefulness of CGP as a screening tool to identify individuals with possible LS, especially when conventional criteria and MSI/MMR testing fail.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Refining the detection of complex rearrangements in 15q15.3 region involving the STRC gene in hereditary hearing loss patients. 改进遗传性听力损失患者STRC基因15q15.3区域复杂重排的检测。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2025-05-08 DOI: 10.1038/s10038-025-01347-9

Sara Alvaro, Daniel Castillo, Jordi Genovés, Erik D Prados, Maurizio Levorato, Anna Albertí, Águeda Díaz, Sara Cardelús, Loreto Martorell

{"title":"Refining the detection of complex rearrangements in 15q15.3 region involving the STRC gene in hereditary hearing loss patients.","authors":"Sara Alvaro, Daniel Castillo, Jordi Genovés, Erik D Prados, Maurizio Levorato, Anna Albertí, Águeda Díaz, Sara Cardelús, Loreto Martorell","doi":"10.1038/s10038-025-01347-9","DOIUrl":"https://doi.org/10.1038/s10038-025-01347-9","url":null,"abstract":"Hearing loss (HL) is the most common sensory disability worldwide, with GJB2-GJB6 connexin alterations (DFNB1) being the most frequent causes of non-syndromic hearing loss (NSHL). Recent studies have also highlighted the STRC gene as a significant contributor to NSHL, with its incidence potentially approaching that of connexin alterations. Despite advances in next-generation sequencing (NGS), molecular diagnosis remains challenging for many NSHL patients, often due to the complexity of analyzing the STRC gene. This is largely attributed to its location in a tandemly duplicated region and the presence of a homologous pseudogene (STRCP1), which complicates its accurate identification. The most common cause of DFNB16 is a homozygous large contiguous gene deletion at 15q15.3, but other copy number variants (CNVs), including both losses and gains, have been less well characterized. Through a combination of techniques we present new data on STRC variants and the diagnosis of 72 DFNB16 patients from 59 families. While the CKMT1B-STRC-CATSPER2 deletion is the most frequent alteration, the improvement of droplet-digital PCR (ddPCR) for refining CNV analysis in the first 16 exons of the gene (99,8% homologous with the pseudogene) has allowed us to identify and better define a higher incidence of previously unclarified complex rearrangements. Additionally, we have identified a direct cis association between the c.4837 G > T;p.(Glu1613*) pathogenic variant and the CATSPER2-CKMT1A-STRCP1 duplication. These findings underscore the important role of ddPCR in identifying CNVs that are difficult to detect through conventional NGS, significantly improving diagnosis and enabling precise genetic counseling for affected families.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Autism and intellectual disability due to a novel gain-of-function mutation in UBE3A. 自闭症和智力残疾是由UBE3A的一种新的功能获得突变引起的。

IF 2.6 3区生物学

Journal of Human Genetics Pub Date : 2025-05-02 DOI: 10.1038/s10038-025-01343-z

Anna M Gunelson, Kwang-Soo Kim, Connolly G Steigerwald, Devorah Segal, Nicolas J Abreu, Jason J Yi

引用次数: 0