American Journal of Medical Genetics Part A最新文献_第4页

Alu-Mediated Deletion of FANCA in Turkish Families With Fanconi Anemia: Evidence of a Founder Effect.

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-03 DOI: 10.1002/ajmg.a.63945

Ceren Damla Durmaz, Fatma Gümrük, Tiraje Celkan, Sule Unal, Arda Çetinkaya

{"title":"Alu-Mediated Deletion of FANCA in Turkish Families With Fanconi Anemia: Evidence of a Founder Effect.","authors":"Ceren Damla Durmaz, Fatma Gümrük, Tiraje Celkan, Sule Unal, Arda Çetinkaya","doi":"10.1002/ajmg.a.63945","DOIUrl":"https://doi.org/10.1002/ajmg.a.63945","url":null,"abstract":"Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome characterized by pancytopenia, increased susceptibility to malignancies, and a spectrum of congenital anomalies. Here, we report on eight affected individuals from six unrelated families with a large Alu-mediated intragenic deletion encompassing exons 6-31 in the FANCA gene, identified as a founder mutation in the Turkish population through haplotype analysis. This deletion, mediated by Alu repeat sequences, underscores the role of repetitive elements in FA pathogenesis. Clinical data revealed variable phenotypic presentations among affected individuals, highlighting the challenge of establishing genotype-phenotype correlations even in the presence of identical FANCA pathogenic variants. We carried out an easy and effective PCR-based diagnostic test for detecting this mutation, enabling precise diagnosis and genetic counseling for affected individuals and their families. This study provides valuable insights into the molecular mechanisms underlying FA pathogenesis and offers a practical approach for genetic diagnosis in affected individuals, particularly those of Turkish descent.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63945"},"PeriodicalIF":1.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764984","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

From Desbuquois Dysplasia to Multiple Epiphyseal Dysplasia: The Clinical Impact of a CANT1 Variant Across Five Unrelated Families.

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-02 DOI: 10.1002/ajmg.a.63950

Tuğba Daşar, Gizem Ürel Demir, Gözde İmren, Gülen Eda Utine, Güney Yilmaz, Pelin Özlem Şimşek Kiper

引用次数: 0

Constitutional Mosaic Pericentromeric Trisomy 8 in a Female Patient With Aplastic Anemia.

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-02 DOI: 10.1002/ajmg.a.63951

Min Gao, Yunjia Chen, Pongtawat Lertwilaiwittaya, Anna C E Hurst, Ali Al-Beshri, Andrew J Carroll, Fady M Mikhail

{"title":"Constitutional Mosaic Pericentromeric Trisomy 8 in a Female Patient With Aplastic Anemia.","authors":"Min Gao, Yunjia Chen, Pongtawat Lertwilaiwittaya, Anna C E Hurst, Ali Al-Beshri, Andrew J Carroll, Fady M Mikhail","doi":"10.1002/ajmg.a.63951","DOIUrl":"https://doi.org/10.1002/ajmg.a.63951","url":null,"abstract":"Aplastic anemia, characterized by pancytopenia and hypoplastic bone marrow, is associated with various acquired cytogenetic abnormalities, including trisomy 8, in 4%-15% of patients. Constitutional mosaic trisomy 8 notably increases the risks for cytopenia and myeloid malignancies. Duplications near chromosome 8 centromere are associated with developmental delays, autism, and trisomy 8p11.21q11.21 correlates with hematologic disorders. We report a 19-year-old female with constitutional mosaic pericentromeric trisomy 8 presenting with menorrhagia, vitamin B12 deficiency, familial short stature, pancytopenia, and bone marrow aplasia. G-banded chromosome and FISH analyses of her bone marrow and blood samples revealed constitutional mosaic pericentromeric trisomy 8. Chromosomal microarray analysis confirmed mosaic duplications in the 8p12q11.21 region spanning 51 OMIM genes, with 16 identified as OMIM morbid genes, and including 9 genes with autosomal dominant inheritance patterns. FGFR1, ASH2L, ANK1, KAT6A, IKBKB, PLAT, and CEBPD are implicated in hematologic disorders, with FGFR1, ASH2L, KAT6A, and IKBKB showing notable triplosensitivity scores. These regions overlap with 13 published cases (12 papers), of which three displayed hematologic disorders, including neutropenia and juvenile myelomonocytic leukemia. Our case underscores the 8p12q11.21 region as a potential causal region for aplastic anemia, emphasizing the need for further investigation of this patient for possible progression to hematologic malignancy.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63951"},"PeriodicalIF":1.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764989","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

Dr. Peter Emil Becker and the Third Reich: Correspondence.

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-30 DOI: 10.1002/ajmg.a.63955

Tilman Becker

引用次数: 0

Implementing a Quality Improvement Initiative to Screen for Dementia in a Down Syndrome Specialty Clinic. 在唐氏综合症专科诊所实施质量改进计划，筛查痴呆症。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-28 DOI: 10.1002/ajmg.a.63948

Stephanie L Santoro, Ayesha Harisinghani, Caroline Bregman, Clorinda Cottrell, Margaret B Pulsifer, Mikayla Shaffer, Amy Torres, Brian G Skotko, Nicolas M Oreskovic

{"title":"Implementing a Quality Improvement Initiative to Screen for Dementia in a Down Syndrome Specialty Clinic.","authors":"Stephanie L Santoro, Ayesha Harisinghani, Caroline Bregman, Clorinda Cottrell, Margaret B Pulsifer, Mikayla Shaffer, Amy Torres, Brian G Skotko, Nicolas M Oreskovic","doi":"10.1002/ajmg.a.63948","DOIUrl":"https://doi.org/10.1002/ajmg.a.63948","url":null,"abstract":"Using quality improvement methods, we aimed to implement a protocol to assess for dementia among adults with Down syndrome (DS). To track implementation, interval retrospective chart review of patients with DS with visits to the Massachusetts General Hospital DS Program (MGH DSP) was conducted quarterly. The impact of a newly implemented protocol created and informed by clinical experts in the MGH DSP including laboratory tests, imaging, referrals, and screening tools for dementia and mental health concerns, was analyzed using statistical process control charts. From December 2021 to December 2022, the MGH DSP developed and implemented a new clinical protocol to screen for dementia in 44 adults with DS, ages 40 and above, at a total of 48 visits. We found high rates of completion of two screening surveys (85% and 81%, respectively) and an 84% adherence to our overall protocol elements by clinical staff. Among those with dementia-like symptoms, medical evaluation was collected and summarized. We show that it is possible to successfully implement a new protocol, including the use of a dementia screener, in line with published evidence-based care guidelines for adults with DS. We present our protocol as one successful approach focused on pre-visit screening for symptoms of dementia and mental health concerns and evaluating for co-occurring medical conditions in adults with DS.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63948"},"PeriodicalIF":1.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738099","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

Health Care Transition Programs for Adolescents and Young Adults With Hereditary Cancer Predisposition: A Scoping Review. 针对有遗传性癌症倾向的青少年的医疗保健过渡计划：范围综述》。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-25 DOI: 10.1002/ajmg.a.63931

Jazmine Gabriel, Tierney Lyons, Victoria Schlieder, Sarah Zultevicz, Bryel Frasch, Thomas W Davis, Adam H Buchanan, Gemme Campbell-Salome

{"title":"Health Care Transition Programs for Adolescents and Young Adults With Hereditary Cancer Predisposition: A Scoping Review.","authors":"Jazmine Gabriel, Tierney Lyons, Victoria Schlieder, Sarah Zultevicz, Bryel Frasch, Thomas W Davis, Adam H Buchanan, Gemme Campbell-Salome","doi":"10.1002/ajmg.a.63931","DOIUrl":"https://doi.org/10.1002/ajmg.a.63931","url":null,"abstract":"Adolescents and young adults (AYA) with increased risk for cancer due to hereditary predisposition, previous cancer treatment, or both are eligible for increased surveillance, chemoprevention, and prophylactic surgery that can improve early detection and prevention of cancers. One way to ensure continuity of cancer prevention care is to support adolescents through the transition from pediatric to adult health care. Yet, there are limited data on the impl ementation of health care transition (HCT) programs for AYA with increased risk for cancer. We conducted a scoping review of the literature on transition programs for AYA at increased risk of cancer due to known germline risk or prior cancer diagnosis, with a focus on implementation factors relevant to designing, implementing, and sustaining a new program. Data from 54 articles were extracted and analyzed using the RE-AIM implementation science framework. Few HCT programs have been implemented for AYA with hereditary cancer syndromes. Several groups have done preimplementation work for future hereditary cancer programs, but programs for cancer survivors are farther along the translational spectrum. We identified implementation factors along the five RE-AIM dimensions to assist preimplementation planning for HCT programs for AYA with increased risk for cancer.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63931"},"PeriodicalIF":1.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714857","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

2q13 Distal Microdeletion: Considering Evidence for an Emerging Syndrome Versus Susceptibility Locus: Twenty-Five New Cases and Review of the Literature. 2q13 远端微缺失：考虑新出现的综合征证据与易感基因位点：25例新病例及文献综述。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-25 DOI: 10.1002/ajmg.a.63946

Eyal Elron, Mordechai Shohat, Lina Basel-Salmon, Sarit Kahana, Reut Matar, Kochav Klein, Ifaat Agmon-Fishman, Merav Gurevitch, Rachel Berger, Dana Brabbing-Goldstein, Michal Levy, Idit Maya

{"title":"2q13 Distal Microdeletion: Considering Evidence for an Emerging Syndrome Versus Susceptibility Locus: Twenty-Five New Cases and Review of the Literature.","authors":"Eyal Elron, Mordechai Shohat, Lina Basel-Salmon, Sarit Kahana, Reut Matar, Kochav Klein, Ifaat Agmon-Fishman, Merav Gurevitch, Rachel Berger, Dana Brabbing-Goldstein, Michal Levy, Idit Maya","doi":"10.1002/ajmg.a.63946","DOIUrl":"https://doi.org/10.1002/ajmg.a.63946","url":null,"abstract":"This study investigates distal 2q13 microdeletion, presenting the largest cohort to date, including prenatal cases, alongside a comprehensive literature review. A retrospective analysis was conducted on distal 2q13 microdeletions from clinical charts and laboratory reports. The cohort was divided into \"clinically indicated\" and \"not-clinically indicated\" groups based on the reason for chromosomal microarray testing. Clinical cases from medical literature were reviewed and compared with our cohort. The study included 25 cases: 17 index patients and 8 family members, with 47% males and 53% females. Of these, 2 were postnatal and 15 were prenatal. In the \"clinically indicated\" group, 35% had abnormalities on prenatal ultrasound, while 65% in the \"not-clinically indicated\" group had no major anomalies. Inheritance was 50% paternal in the \"clinically indicated\" group, and in the \"not-clinically indicated\" group, 44% paternal, 22% maternal, and 33% de novo. Symptoms varied from asymptomatic to severe developmental issues. Literature review identified 51 postnatal cases, with intellectual disability, and dysmorphism being common features. Familial cases showed 20% de novo, 20% maternal, 21.5% paternal, and 40% unknown inheritance. Distal 2q13 microdeletion is linked to cognitive impairment risk and should be reported in test results based on parental preferences, requiring special considerations for clinical classification and reporting.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63946"},"PeriodicalIF":1.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714854","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

De Novo Balanced Translocations Disrupting the FBN1 Gene Diagnosed by Genome Sequencing: An Uncommon Cause of Marfan Syndrome Modifying Genetic Counseling. 通过基因组测序诊断出干扰 FBN1 基因的新平衡易位：马凡综合征的一个不常见病因，改变遗传咨询。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-25 DOI: 10.1002/ajmg.a.63923

C Racine, P Callier, R Touraine, A Vitobello, N Hanna, P Arnaud, G Jondeau, C Boileau, C Thauvin-Robinet, I Creveaux, V Gatinois, M Willems, L Faivre

{"title":"De Novo Balanced Translocations Disrupting the FBN1 Gene Diagnosed by Genome Sequencing: An Uncommon Cause of Marfan Syndrome Modifying Genetic Counseling.","authors":"C Racine, P Callier, R Touraine, A Vitobello, N Hanna, P Arnaud, G Jondeau, C Boileau, C Thauvin-Robinet, I Creveaux, V Gatinois, M Willems, L Faivre","doi":"10.1002/ajmg.a.63923","DOIUrl":"https://doi.org/10.1002/ajmg.a.63923","url":null,"abstract":"Marfan syndrome (MFS) is a well-characterized rare genetic connective tissue disorder. The features of MFS are primarily skeletal, ocular, and cardiovascular and are mainly caused by single-nucleotide variants (SNVs) in the FBN1 gene (MIM#134797) located on chromosome 15q21.1. We describe two patients, a 26-year-old male and a 10-year-old female from unrelated distinct families, with clinically diagnosed sporadic MFS. After years of unsuccessful molecular diagnosis for genetic counseling purposes, genome sequencing was performed and revealed a balanced translocation in both patients: de novo t(9;15)(p13.3;q21.1) translocation in the male patient, and de novo t(15;16)(q21.1;p13.13) translocation in the female patient, respectively, disrupting intron 40 and 45 of FBN1. The other breakpoints were not clinically relevant. These translocations were confirmed by specific fluorescence in situ hybridization probes and conventional karyotyping. In the literature, only one family has been described, leading to four cases of MFS caused by balanced translocations. Genetic counseling for balanced translocations differs from SNVs and even interstitial deletions since it is not restricted to MFS recurrence, but also involves the risk of unbalanced gametes, leading to miscarriage or unbalanced progeny. In case of clinical certainty, MFS patients should be screened for balanced translocations to ensure appropriate genetic counseling.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63923"},"PeriodicalIF":1.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708520","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

An Extended Phenotype of PPP1R13L Cardiocutaneous Syndrome. PPP1R13L心皮综合征的扩展表型

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-23 DOI: 10.1002/ajmg.a.63932

Alicia Coudert, Julien Thevenon, Quentin Testard, Véronique Satre, Radu Harbuz, Patrice Bouvagnet, Pierre-Yves Rabattu, Charles Coutton, Pauline Le Tanno

引用次数: 0

Quality of Life in Short Stature Children With Skeletal Dysplasia: A Cross Sectional Study Using the Quality of Life in Short Stature Youth Questionnaire. 患有骨骼发育不良的矮身材儿童的生活质量：使用矮身材青少年生活质量问卷进行的横断面研究。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-21 DOI: 10.1002/ajmg.a.63942

Yasunari Kamiya, Masaki Matsushita, Kenichi Mishima, Kenta Sawamura, Hiroshi Kitoh

{"title":"Quality of Life in Short Stature Children With Skeletal Dysplasia: A Cross Sectional Study Using the Quality of Life in Short Stature Youth Questionnaire.","authors":"Yasunari Kamiya, Masaki Matsushita, Kenichi Mishima, Kenta Sawamura, Hiroshi Kitoh","doi":"10.1002/ajmg.a.63942","DOIUrl":"https://doi.org/10.1002/ajmg.a.63942","url":null,"abstract":"Patients with skeletal dysplasia, including achondroplasia (ACH) and osteogenesis imperfecta (OI), exhibit a variety of short stature, which affect various aspects of their quality of life (QoL). The QoL of adult patients with skeletal dysplasia have been reported; however, research on QoL in children remains limited. The QoL in Short Stature Youth (QoLISSY) is a QoL survey tool developed specifically for short stature children and adolescent. We assessed the QoLISSY scores in children with various skeletal dysplasias presenting with short stature and compared the scores among ACH, OI, and other dysplasias. Forty and 72 questionnaires were sent to the children with various skeletal dysplasias and their parents, respectively, and 24 and 54 valid questionnaires, respectively, were collected. There were no significant differences in age, sex, or height between the patients with ACH, OI, and other skeletal dysplasias. Parents' social, emotional, and total QoL scores were significantly lower in the ACH group than in the OI group. A sub-analysis revealed that the height standard deviation score did not correlate with the QoLISSY scores in all groups except for the belief score of OI parents.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63942"},"PeriodicalIF":1.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680378","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