American Journal of Medical Genetics Part A最新文献_第7页

Integrated Genomic Approach: A Five Exon Intragenic Deletion in UNC80 Combines With a Novel Splice Variant to Cause IHPRF2 Syndrome in an Italian Family. 整合基因组方法：在一个意大利家庭中，UNC80基因的5外显子基因内缺失与一种新的剪接变体结合导致IHPRF2综合征。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-08-13 DOI: 10.1002/ajmg.a.64224

Mario Benvenuto, Dora Varvara, Massimo Carella, Pietro Palumbo, Luigi Bisceglia, Lucia Micale, Marco Castori, Orazio Palumbo

{"title":"Integrated Genomic Approach: A Five Exon Intragenic Deletion in UNC80 Combines With a Novel Splice Variant to Cause IHPRF2 Syndrome in an Italian Family.","authors":"Mario Benvenuto, Dora Varvara, Massimo Carella, Pietro Palumbo, Luigi Bisceglia, Lucia Micale, Marco Castori, Orazio Palumbo","doi":"10.1002/ajmg.a.64224","DOIUrl":"https://doi.org/10.1002/ajmg.a.64224","url":null,"abstract":"Rare diseases impact ~6%-8% of the population, thus constituting an issue for public health worldwide. The increasing application of genomic technologies in the routine diagnosis of these conditions is documenting the need to integrate multiple techniques in the most complex cases. We describe a 14-year-old boy and his 4-year-old sister, both presenting with neonatal hypotonia, severe global developmental delay, major feeding difficulties with the need for assisted nutrition, inability to speak and walk autonomously, epilepsy, central sleep apnea, and facial dysmorphism, in whom exome sequencing revealed the novel c.798 + 1G>T variant in the UNC80 gene at the heterozygous state. While reverse phenotyping was compatible with a clinical diagnosis of infantile hypotonia, psychomotor retardation, and characteristic facies type 2 syndrome, chromosomal microarray disclosed a microdeletion involving 5 exons (40-44) in the other allele. Our findings expand the mutational repertoire of UNC80 and demonstrate that infantile hypotonia, psychomotor retardation, and characteristic facies type 2 syndrome may also be caused by intragenic copy number variations. The combination of multiple techniques, also comprising exon-level resolution array, is a resource in real-world diagnostics of rare diseases.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64224"},"PeriodicalIF":1.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Prenatal Diagnosis of Hartsfield Syndrome in the Fetus With Isolated Ectrodactyly Caused by a Novel Variant in FGFR1. 由FGFR1新变异引起的孤立性外指畸形胎儿Hartsfield综合征的产前诊断

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-08-13 DOI: 10.1002/ajmg.a.64226

Jun An, Sihui Wu, Kexin Guo, Hao Chen, Chun Yang, Fengchang Qiao, Ping Hu

{"title":"Prenatal Diagnosis of Hartsfield Syndrome in the Fetus With Isolated Ectrodactyly Caused by a Novel Variant in FGFR1.","authors":"Jun An, Sihui Wu, Kexin Guo, Hao Chen, Chun Yang, Fengchang Qiao, Ping Hu","doi":"10.1002/ajmg.a.64226","DOIUrl":"https://doi.org/10.1002/ajmg.a.64226","url":null,"abstract":"Molecular genetic testing was performed on a fetus with ectrodactyly of the right foot to clarify the pathogenic cause and provide evidence for prenatal counseling. Trio whole-exome sequencing (trio-WES) was performed on the fetus and his parents to identify the underlying genetic cause. Candidate variants were validated by Sanger sequencing, and their molecular effects were analyzed through minigene assays. Trio-WES identified a novel heterozygous variant (c.1977+1G>C) in FGFR1, which is consistent with FGFR1-related Hartsfield syndrome (HS; OMIM#615465). Sanger sequencing confirmed that this variant was de novo. The minigene assay revealed that all variants (c.1977+1G>C, c.1977+1G>A, and c.1977+1G>T) at the splice site generated two aberrant splicing events: (1) complete retention of intron 14, leading to a frameshift and premature termination codon; and (2) skipping of exon 14, causing an in-frame deletion of 41 amino acids. These events collectively impaired the function of the FGFR1 protein's tyrosine kinase domain. To our knowledge, prenatal reports of FGFR1-related HS remain extremely limited, and this is the first molecularly confirmed prenatal diagnosis of HS in China. The findings not only expand the mutational spectrum of HS but also provide genetic counseling and reproductive guidance for this family.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64226"},"PeriodicalIF":1.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-08-13 DOI: 10.1002/ajmg.a.64222

Adriana Gomes, Álvaro Martín-Rodríguez, Neil M Shah, Li Hong, Lynne M Bird

引用次数: 0

Generating Advancements in Longitudinal Analysis in X and Y Variations: Rationale, Methods, and Diagnostic Characteristics for the GALAXY Registry. 在X和Y变异的纵向分析中取得进展：GALAXY登记的基本原理、方法和诊断特征。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-08-13 DOI: 10.1002/ajmg.a.64214

Alexandra Carl, Samantha Bothwell, Karli Swenson, Ryan Bregante, Lilian Cohen, Virginia Cover, Anna Dawczyk, Gail Decker, Stephen B Gerken, David Hong, Susan Howell, Armin Raznahan, Alan D Rogol, Nicole Tartaglia, Shanlee Davis

{"title":"Generating Advancements in Longitudinal Analysis in X and Y Variations: Rationale, Methods, and Diagnostic Characteristics for the GALAXY Registry.","authors":"Alexandra Carl, Samantha Bothwell, Karli Swenson, Ryan Bregante, Lilian Cohen, Virginia Cover, Anna Dawczyk, Gail Decker, Stephen B Gerken, David Hong, Susan Howell, Armin Raznahan, Alan D Rogol, Nicole Tartaglia, Shanlee Davis","doi":"10.1002/ajmg.a.64214","DOIUrl":"https://doi.org/10.1002/ajmg.a.64214","url":null,"abstract":"Sex chromosome aneuploidies (SCAs) are a family of genetic disorders that result from an atypical number of X and/or Y chromosomes. SCAs are the most common chromosomal abnormality, affecting ~1/400 live births, yet are often underdiagnosed, leading to over-representation of more severely impacted individuals in many clinical studies. In addition to this ascertainment bias, existing work in SCAs has also been limited by low geographic and demographic diversity. To address these limitations, we have created the Generating Advancements with Longitudinal Analysis in X and Y variations (GALAXY) Registry. Through prioritizing sustainability, transparency, and minimizing participant burden, the overarching goal of the GALAXY Registry is to improve health outcomes for individuals with SCAs by serving as an infrastructure for future SCA research based on a large, heterogeneous, and longitudinal sample. To date, GALAXY has accrued 335 verified SCA participants with an average accrual of 11.2 participants/month (6.7 47,XXY, 1.9 47,XXX, 2.0 47,XYY, 3.2 48,XXYY, 1.8 48,XXXY, and 1.3 Other). Demographic data between those identified to have SCA prenatally (predominantly cell-free DNA screening) differ from those diagnosed postnatally for insurance status, age at enrollment, genetic test type, and reason for SCA diagnosis. Next steps include targeted recruitment of underrepresented groups (e.g., non-47,XXY karyotypes, older adults, minoritized individuals), extraction of medical record data into the registry, international expansion, and continued engagement with the SCA community. As a collaboration between clinician investigators and the SCA community, the GALAXY Registry is a powerful resource for future patient-centered clinical research.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64214"},"PeriodicalIF":1.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Assessing Pubertal Timing, Duration, and Related Characteristics in ASXL-Related Disorders: A Cross-Sectional Caregiver Survey Analysis. 评估asxl相关障碍的青春期时间、持续时间和相关特征：一项横断面护理者调查分析。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-08-13 DOI: 10.1002/ajmg.a.64216

Amanda Piring, Rebecca Hicks, Julia Sloan, Estefania Ramires-Sanchez, Bianca E Russell

{"title":"Assessing Pubertal Timing, Duration, and Related Characteristics in ASXL-Related Disorders: A Cross-Sectional Caregiver Survey Analysis.","authors":"Amanda Piring, Rebecca Hicks, Julia Sloan, Estefania Ramires-Sanchez, Bianca E Russell","doi":"10.1002/ajmg.a.64216","DOIUrl":"10.1002/ajmg.a.64216","url":null,"abstract":"Limited studies have been conducted on pubertal development in populations with pre-existing medical conditions. More than 20-fold increased risk of early puberty has been reported in neurodevelopmental disorders; however, this is a heterogeneous group. There have been limited past studies examining the timing, duration, or characteristics of pubertal or menstrual cycle development in patients with ASXL-related disorders. This study aimed to gather empirical cross-sectional parent survey data regarding pubertal development in adolescents diagnosed with Bohring-Opitz syndrome (BOS) (ASXL1), Shashi-Pena syndrome (SPS) (ASXL2), or Bainbridge-Ropers syndrome (BRS) (ASXL3). Our findings showed evidence for parental and perceived provider concern for premature pubarche and possible precocious puberty (PP) in BOS (ASXL1) males and females. Findings between the BOS (ASXL1) and BRS (ASXL3) individuals differed, representing distinct pubertal phenotypes within these populations. Notable trends toward premature development may warrant a low threshold for pediatric endocrinological evaluation in this population. The characterization and description of a pubertal profile for the ASXL-related syndromes can help inform providers and parents when navigating this stage of development. Our study findings also highlight the need for prospective natural history studies to further define the contribution of pubertal development to the ASXL disorders phenotypes.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64216"},"PeriodicalIF":1.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

First Patient Successfully Receives Custom Gene Therapy 首例患者成功接受定制基因治疗

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-08-11 DOI: 10.1002/ajmg.a.63758

引用次数: 0

Cover Image, Volume 197A, Number 9, September 2025 封面图片，197A卷，第9期，2025年9月

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-08-11 DOI: 10.1002/ajmg.a.64218

引用次数: 0

Fetal Mutations Responsible for 1 in 136 Pregnancy Losses 胎儿突变导致136例妊娠失败

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-08-11 DOI: 10.1002/ajmg.a.63760

引用次数: 0

Table of Contents, Volume 197A, Number 9, September 2025 目录，197A卷，第9号，2025年9月

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-08-11 DOI: 10.1002/ajmg.a.63763

引用次数: 0

Down Syndrome in Maternity Care: Mothers' Experiences of Prenatal Screening. 唐氏综合症在产科护理：母亲产前筛查的经验。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-08-09 DOI: 10.1002/ajmg.a.64206

Tamar Rutter, Richard Hastings, Nicola Enoch, Samantha Flynn, Matthew Randell, Chris Stinton

{"title":"Down Syndrome in Maternity Care: Mothers' Experiences of Prenatal Screening.","authors":"Tamar Rutter, Richard Hastings, Nicola Enoch, Samantha Flynn, Matthew Randell, Chris Stinton","doi":"10.1002/ajmg.a.64206","DOIUrl":"https://doi.org/10.1002/ajmg.a.64206","url":null,"abstract":"Prenatal screening for Down syndrome (DS) is offered to expectant parents receiving antenatal care in many countries, with an emphasis on providing parents with the opportunity to make informed choices about their pregnancy. We examined experiences of prenatal screening among mothers of children with DS living in England, Scotland, or Wales. Mothers (N = 317) of a child with DS born between 2019 and 2022 responded to an online survey and answered closed and open-ended questions about their experiences of being offered initial screening and non-invasive prenatal testing, and of receiving screening results. The findings from quantitative and qualitative analyses indicated that while most mothers understood screening was optional, many accepted initial screening with little consideration and most perceived it as routine. Many mothers reported receiving insufficient information about DS and limited support to help them make sense of screening results. Many mothers reported that screening results were not presented neutrally, and some highlighted how communication which reflected negative attitudes or assumptions about DS was highly memorable and impactful. The importance of personalized discussion to support mothers' understanding of screening, and to legitimize the option of declining screening tests, is discussed. The findings highlight the importance of a neutral approach to the delivery of both higher and lower chance screening results and of welcoming a diversity of choices.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64206"},"PeriodicalIF":1.7,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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