Therapeutic strategies for aberrant splicing in cancer and genetic disorders
Clin Genet. 2024 Jan 2. doi: 10.1111/cge.14478. Online ahead of print.ABSTRACTAccurate pre-mRNA splicing is essential for proper protein translation; however, aberrant splicing is commonly observed in the context of cancer and genetic disorders. Notably, in genetic diseases, these splicing abnormalities often play a pivotal role. Substantial challenges persist in accurately identifying and classifying disease-induced aberrant splicing, as well as in development of targeted therapeutic strategies. In this review, we examine prevalent forms of aberrant splicing and explore potential therapeutic approaches aimed at addressing...
Source: Clinical Genetics - January 2, 2024 Category: Genetics & Stem Cells Authors: Wenhua Shi Jingqun Tang Juanjuan Xiang Source Type: research
Identifying candidate genes underlying isolated congenital anosmia
This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function.PMID:38148624 | DOI:10.1111/cge.14470 (Source: Clinical Genetics)
Source: Clinical Genetics - December 27, 2023 Category: Genetics & Stem Cells Authors: Marissa L Kamarck Casey Trimmer Nicolle R Murphy Kristen M Gregory Diogo Manoel Darren W Logan Luis R Saraiva Joel D Mainland Source Type: research
SAM domain variants of EPHB4 associated with aberrant signaling are linked to lymphatic-related fetal hydrops and facial dysmorphology
Clin Genet. 2023 Dec 27. doi: 10.1111/cge.14467. Online ahead of print.ABSTRACTVariants in EPHB4 (Ephrin type B receptor 4), a transmembrane tyrosine kinase receptor, have been identified in individuals with various vascular anomalies including Capillary Malformation-Arteriovenous Malformation syndrome 2 and lymphatic-related (non-immune) fetal hydrops (LRHF). Here, we identify two novel variants in EPHB4 that disrupt the SAM domain in two unrelated individuals. Proband 1 presented within the LRHF phenotypic spectrum with hydrops, and proband 2 presented with large nuchal translucency prenatally that spontaneously resolved...
Source: Clinical Genetics - December 27, 2023 Category: Genetics & Stem Cells Authors: Kara Vanden Broek Jae-Ryeon Ryu Renee Perrier Amanda V Tyndall Sarah J Childs Ping Yee Billie Au Source Type: research
Identifying candidate genes underlying isolated congenital anosmia
This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function.PMID:38148624 | DOI:10.1111/cge.14470 (Source: Clinical Genetics)
Source: Clinical Genetics - December 27, 2023 Category: Genetics & Stem Cells Authors: Marissa L Kamarck Casey Trimmer Nicolle R Murphy Kristen M Gregory Diogo Manoel Darren W Logan Luis R Saraiva Joel D Mainland Source Type: research
SAM domain variants of EPHB4 associated with aberrant signaling are linked to lymphatic-related fetal hydrops and facial dysmorphology
Clin Genet. 2023 Dec 27. doi: 10.1111/cge.14467. Online ahead of print.ABSTRACTVariants in EPHB4 (Ephrin type B receptor 4), a transmembrane tyrosine kinase receptor, have been identified in individuals with various vascular anomalies including Capillary Malformation-Arteriovenous Malformation syndrome 2 and lymphatic-related (non-immune) fetal hydrops (LRHF). Here, we identify two novel variants in EPHB4 that disrupt the SAM domain in two unrelated individuals. Proband 1 presented within the LRHF phenotypic spectrum with hydrops, and proband 2 presented with large nuchal translucency prenatally that spontaneously resolved...
Source: Clinical Genetics - December 27, 2023 Category: Genetics & Stem Cells Authors: Kara Vanden Broek Jae-Ryeon Ryu Renee Perrier Amanda V Tyndall Sarah J Childs Ping Yee Billie Au Source Type: research
Identifying candidate genes underlying isolated congenital anosmia
This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function.PMID:38148624 | DOI:10.1111/cge.14470 (Source: Clinical Genetics)
Source: Clinical Genetics - December 27, 2023 Category: Genetics & Stem Cells Authors: Marissa L Kamarck Casey Trimmer Nicolle R Murphy Kristen M Gregory Diogo Manoel Darren W Logan Luis R Saraiva Joel D Mainland Source Type: research
SAM domain variants of EPHB4 associated with aberrant signaling are linked to lymphatic-related fetal hydrops and facial dysmorphology
Clin Genet. 2023 Dec 27. doi: 10.1111/cge.14467. Online ahead of print.ABSTRACTVariants in EPHB4 (Ephrin type B receptor 4), a transmembrane tyrosine kinase receptor, have been identified in individuals with various vascular anomalies including Capillary Malformation-Arteriovenous Malformation syndrome 2 and lymphatic-related (non-immune) fetal hydrops (LRHF). Here, we identify two novel variants in EPHB4 that disrupt the SAM domain in two unrelated individuals. Proband 1 presented within the LRHF phenotypic spectrum with hydrops, and proband 2 presented with large nuchal translucency prenatally that spontaneously resolved...
Source: Clinical Genetics - December 27, 2023 Category: Genetics & Stem Cells Authors: Kara Vanden Broek Jae-Ryeon Ryu Renee Perrier Amanda V Tyndall Sarah J Childs Ping Yee Billie Au Source Type: research
Identifying candidate genes underlying isolated congenital anosmia
This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function.PMID:38148624 | DOI:10.1111/cge.14470 (Source: Clinical Genetics)
Source: Clinical Genetics - December 27, 2023 Category: Genetics & Stem Cells Authors: Marissa L Kamarck Casey Trimmer Nicolle R Murphy Kristen M Gregory Diogo Manoel Darren W Logan Luis R Saraiva Joel D Mainland Source Type: research
SAM domain variants of EPHB4 associated with aberrant signaling are linked to lymphatic-related fetal hydrops and facial dysmorphology
Clin Genet. 2023 Dec 27. doi: 10.1111/cge.14467. Online ahead of print.ABSTRACTVariants in EPHB4 (Ephrin type B receptor 4), a transmembrane tyrosine kinase receptor, have been identified in individuals with various vascular anomalies including Capillary Malformation-Arteriovenous Malformation syndrome 2 and lymphatic-related (non-immune) fetal hydrops (LRHF). Here, we identify two novel variants in EPHB4 that disrupt the SAM domain in two unrelated individuals. Proband 1 presented within the LRHF phenotypic spectrum with hydrops, and proband 2 presented with large nuchal translucency prenatally that spontaneously resolved...
Source: Clinical Genetics - December 27, 2023 Category: Genetics & Stem Cells Authors: Kara Vanden Broek Jae-Ryeon Ryu Renee Perrier Amanda V Tyndall Sarah J Childs Ping Yee Billie Au Source Type: research
Identifying candidate genes underlying isolated congenital anosmia
This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function.PMID:38148624 | DOI:10.1111/cge.14470 (Source: Clinical Genetics)
Source: Clinical Genetics - December 27, 2023 Category: Genetics & Stem Cells Authors: Marissa L Kamarck Casey Trimmer Nicolle R Murphy Kristen M Gregory Diogo Manoel Darren W Logan Luis R Saraiva Joel D Mainland Source Type: research
SAM domain variants of EPHB4 associated with aberrant signaling are linked to lymphatic-related fetal hydrops and facial dysmorphology
Clin Genet. 2023 Dec 27. doi: 10.1111/cge.14467. Online ahead of print.ABSTRACTVariants in EPHB4 (Ephrin type B receptor 4), a transmembrane tyrosine kinase receptor, have been identified in individuals with various vascular anomalies including Capillary Malformation-Arteriovenous Malformation syndrome 2 and lymphatic-related (non-immune) fetal hydrops (LRHF). Here, we identify two novel variants in EPHB4 that disrupt the SAM domain in two unrelated individuals. Proband 1 presented within the LRHF phenotypic spectrum with hydrops, and proband 2 presented with large nuchal translucency prenatally that spontaneously resolved...
Source: Clinical Genetics - December 27, 2023 Category: Genetics & Stem Cells Authors: Kara Vanden Broek Jae-Ryeon Ryu Renee Perrier Amanda V Tyndall Sarah J Childs Ping Yee Billie Au Source Type: research
A bi-allelic REC114 loss-of-function variant causes meiotic arrest and nonobstructive azoospermia
Clin Genet. 2023 Dec 26. doi: 10.1111/cge.14473. Online ahead of print.ABSTRACTNonobstructive azoospermia (NOA), the most severe manifestation of male infertility, lacks a comprehensive understanding of its genetic etiology. Here, a bi-allelic loss-of-function variant in REC114 (c.568C > T: p.Gln190*) were identified through whole exome sequencing (WES) in a Chinese NOA patient. Testicular histopathological analysis and meiotic chromosomal spread analysis were conducted to assess the stage of spermatogenesis arrested. Co-immunoprecipitation (Co-IP) and Western blot (WB) were used to investigate the influence of variant ...
Source: Clinical Genetics - December 26, 2023 Category: Genetics & Stem Cells Authors: Shuai Xu Jingpeng Zhao Feng Gao Yuxiang Zhang Jiaqiang Luo Chenwang Zhang Ruhui Tian Erlei Zhi Jianxiong Zhang Furong Bai Hongfang Sun Fujun Zhao Yuhua Huang Peng Li Liren Jiang Zheng Li Chencheng Yao Zhi Zhou Source Type: research
Epidemiological and clinical features of malignant hyperthermia: A scoping review
Clin Genet. 2023 Dec 26. doi: 10.1111/cge.14475. Online ahead of print.ABSTRACTMalignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of...
Source: Clinical Genetics - December 26, 2023 Category: Genetics & Stem Cells Authors: Zhukai Cong Tingting Wan Jiechu Wang Luyang Feng Cathy Cao Zhengqian Li Xiaoxiao Wang Yongzheng Han Yang Zhou Ya Gao Jing Zhang Yinyin Qu Xiangyang Guo Source Type: research
Spermatozoa in mice lacking the nucleoporin NUP210L show defects in head shape and motility but not in nuclear compaction or histone replacement
Clin Genet. 2023 Dec 21. doi: 10.1111/cge.14468. Online ahead of print.ABSTRACTBiallelic loss-of-function mutation of NUP210L, encoding a testis-specific nucleoporin, has been reported in an infertile man whose spermatozoa show uncondensed heads and histone retention. Mice with a homozygous transgene intronic insertion in Nup210l were infertile but spermatozoa had condensed heads. Expression from this insertion allele is undefined, however, and residual NUP210L production could underlie the milder phenotype. To resolve this issue, we have created Nup210lem1Mjmm , a null allele of Nup210l, in the mouse. Nup210lem1Mjmm homoz...
Source: Clinical Genetics - December 21, 2023 Category: Genetics & Stem Cells Authors: Maha Al Dala Ali Guy Longepied Aurore Nicolet Catherine Metzler-Guillemain Michael J Mitchell Source Type: research
Spermatozoa in mice lacking the nucleoporin NUP210L show defects in head shape and motility but not in nuclear compaction or histone replacement
Clin Genet. 2023 Dec 21. doi: 10.1111/cge.14468. Online ahead of print.ABSTRACTBiallelic loss-of-function mutation of NUP210L, encoding a testis-specific nucleoporin, has been reported in an infertile man whose spermatozoa show uncondensed heads and histone retention. Mice with a homozygous transgene intronic insertion in Nup210l were infertile but spermatozoa had condensed heads. Expression from this insertion allele is undefined, however, and residual NUP210L production could underlie the milder phenotype. To resolve this issue, we have created Nup210lem1Mjmm , a null allele of Nup210l, in the mouse. Nup210lem1Mjmm homoz...
Source: Clinical Genetics - December 21, 2023 Category: Genetics & Stem Cells Authors: Maha Al Dala Ali Guy Longepied Aurore Nicolet Catherine Metzler-Guillemain Michael J Mitchell Source Type: research
