American Journal of Medical Genetics Part A最新文献_第10页

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

Chronic Catatonia in an Individual With a De Novo Missense SHANK1 Variant. 一名患有新发缺义 SHANK1 变异的患者的慢性紧张症

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.63943

Paige M Dahlberg, Holly K Harris, J Lloyd Holder

引用次数: 0

From Clinical Observation to Genetic Confirmation: Somatic Mosaic Mutations in RHOA on Ectodermal Dysplasia With Multi-System Involvement. 从临床观察到基因确认：外胚层发育不良伴多系统参与的 RHOA 基因体细胞马赛克突变。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-20 DOI: 10.1002/ajmg.a.63934

Enise Avci Durmusalioglu, Yusuf Can Dogan, Turkan Turkut Tan, Dilsah Cogulu, Esra Isik, Ozgur Cogulu, Tahir Atik

{"title":"From Clinical Observation to Genetic Confirmation: Somatic Mosaic Mutations in RHOA on Ectodermal Dysplasia With Multi-System Involvement.","authors":"Enise Avci Durmusalioglu, Yusuf Can Dogan, Turkan Turkut Tan, Dilsah Cogulu, Esra Isik, Ozgur Cogulu, Tahir Atik","doi":"10.1002/ajmg.a.63934","DOIUrl":"https://doi.org/10.1002/ajmg.a.63934","url":null,"abstract":"Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies (EDFAOB) is a rare neuroectodermal syndrome caused by somatic mosaic mutations in the RHOA gene. It presents with linear skin hypopigmentation, facial and limb asymmetry, dental and acral anomalies, and leukoencephalopathy, generally preserving intellectual and neurological functions. We report two cases of EDFAOB. Both cases initially presented with notable facial-body asymmetry, thin hair, dental issues, digital anomalies, and Blaschko's lines-aligned hypopigmentation. A 6-year-old girl exhibited esotropia, visual center atrophy, and bilateral white matter hyperintensities on MRI. A 10-year-old girl had unilateral hyperintense lesions in the left cerebral hemisphere on MRI. Both had normal neuromotor development without intellectual impairment. RHOA gene sequencing from hypopigmented skin biopsies revealed the c.139G > A (p.Glu47Lys) mutation, with allele fractions of 20% and 10%, respectively, absent in blood leukocytes and parental DNA. These cases highlight the clinical and genetic features of EDFAOB and underscore the importance of thorough clinical evaluation to guide precise genetic testing. The identification of mutations exclusively in affected tissues supports a postzygotic mosaic distribution, refining the diagnostic approach for this syndrome.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63934"},"PeriodicalIF":1.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674817","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

Long-Term Health Outcomes of Individuals With Pseudodeficiency Alleles in IDUA May Inform Newborn Screening Practices for Mucopolysaccharidosis Type I. IDUA假缺失等位基因个体的长期健康结果可为I型黏多醣症的新生儿筛查实践提供参考。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-19 DOI: 10.1002/ajmg.a.63940

Lauren O Grady, Emilie S Zoltick, Hana Zouk, Wei He, Emma Perez, Lorne Clarke, Jessica Gold, Alanna Strong, Inderneel Sahai, Julie Yeo, Robert C Green, Amel Karaa, Nina B Gold

{"title":"Long-Term Health Outcomes of Individuals With Pseudodeficiency Alleles in IDUA May Inform Newborn Screening Practices for Mucopolysaccharidosis Type I.","authors":"Lauren O Grady, Emilie S Zoltick, Hana Zouk, Wei He, Emma Perez, Lorne Clarke, Jessica Gold, Alanna Strong, Inderneel Sahai, Julie Yeo, Robert C Green, Amel Karaa, Nina B Gold","doi":"10.1002/ajmg.a.63940","DOIUrl":"10.1002/ajmg.a.63940","url":null,"abstract":"Mucopolysaccharidosis type I (MPS I), a lysosomal disorder caused by variants in IDUA, was added to the Recommended Uniform Screening Panel for newborn screening in 2016. Positive screening results for MPS I are commonly due to variants known as \"pseudodeficiency alleles,\" which decrease in vitro alpha-L-iduronidase enzyme activity but are thought to provide sufficient in vivo activity. Despite the historic assumption that these variants are biologically benign, the possibility that they could give rise to complex, multigenic, or attenuated phenotypes has not been systemically evaluated in adults. We completed a retrospective matched cohort study using a hospital-based biorepository with data from 65,309 participants, we identified 1803 individuals harboring homozygous IDUA pseudodeficiency alleles. Using electronic medical records (EMR), we compared the prevalence of features of MPS I in participants with homozygous pseudodeficiency alleles to a cohort of matched control participants. We found no clinically relevant significant differences between cases and controls nor genotype-phenotype associations across four alleles. These findings provide empiric support that adults with homozygous IDUA pseudodeficiency alleles are unlikely to develop mild symptoms of disease compared with controls. This study provides a proof-of-concept model for other nonclassical disease variants related to other inherited metabolic disorders, which is necessary as newborn screening expands.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63940"},"PeriodicalIF":1.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666778","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

A Novel De Novo Splice Acceptor Variant in BICD2 Is Associated With Spinal Muscular Atrophy. BICD2 中的一种新型新拼接受体变异与脊髓肌肉萎缩有关。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-19 DOI: 10.1002/ajmg.a.63944

Giulia F Del Gobbo, Xueqi Wang, Stella K MacDonald, Yijing Liang, Hugh J McMillan, Gabrielle Lemire, Kym M Boycott

引用次数: 0

The Glu86 Residue in TBX4 Proves Critical for Human Lung Development. TBX4中的Glu86残基对人类肺部发育至关重要

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-17 DOI: 10.1002/ajmg.a.63936

Przemyslaw Szafranski, Tomasz Gambin, Gail Deutsch, Salma A Nassef, Mary Clay Bailey, Debra L Kearney, Paweł Stankiewicz

{"title":"The Glu86 Residue in TBX4 Proves Critical for Human Lung Development.","authors":"Przemyslaw Szafranski, Tomasz Gambin, Gail Deutsch, Salma A Nassef, Mary Clay Bailey, Debra L Kearney, Paweł Stankiewicz","doi":"10.1002/ajmg.a.63936","DOIUrl":"10.1002/ajmg.a.63936","url":null,"abstract":"T-box transcription factors are a group of evolutionarily conserved T-box-containing regulators of mesoderm specification and development. Heterozygous single nucleotide variants (SNVs) or copy-number variant (CNV) deletions involving dosage-sensitive TBX4 have been associated with pulmonary arterial hypertension (PAH), ischiocoxopodopatellar syndrome with or without PAH, and lethal lung developmental disorders (LLDDs), including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD), and other unspecified primary pulmonary hypoplasias. Loss- and gain-of-function variants have been proposed to cause pediatric PAH and LLDDs, and adult forms of PAH, respectively. Of more than 50 missense SNVs scattered across the entire TBX4, only three have been reported in patients with LLDDs, all mapping to the T-box domain. Here, we report a recurrence of a pathogenic substitution Glu86Lys identified in an unrelated patient with AcDys. In silico predictions of the conformational changes of TBX4 resulting from this and another substitution, Glu86Gln, suggest the loss of most intermolecular hydrogen bonds involving residue 86, including those with Tyr230 that directly interact with DNA. Functional assays on the TBX4 variants in fetal lung fibroblasts confirmed their deleterious character. We propose that Glu86 is critically involved in maintaining TBX4 structure and function essential for airway branching during early stages of human lung development. Substitutions of this residue may act in a dominant negative manner, leading to AcDys and CAD.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63936"},"PeriodicalIF":1.7,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646662","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

Insights From a Novel Splicing Variant and Recurrent Arginine Variants in the CHD3 Gene Causing Snijders Blok-Campeau Syndrome. 从导致 Snijders Blok-Campeau 综合征的 CHD3 基因中的新型剪接变异和复发性精氨酸变异中获得启示。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-14 DOI: 10.1002/ajmg.a.63930

Xiaoling Tie, Fengyu Che, Siting Liu, Lidangzhi Mo, Liyu Zhang, Benchang Li, Ying Yang

{"title":"Insights From a Novel Splicing Variant and Recurrent Arginine Variants in the CHD3 Gene Causing Snijders Blok-Campeau Syndrome.","authors":"Xiaoling Tie, Fengyu Che, Siting Liu, Lidangzhi Mo, Liyu Zhang, Benchang Li, Ying Yang","doi":"10.1002/ajmg.a.63930","DOIUrl":"10.1002/ajmg.a.63930","url":null,"abstract":"Snijders Blok-Campeau syndrome (SNIBCPS, OMIM#618205) is an autosomal dominant neurodevelopmental disorder attributed to pathogenic variants in the chromodomain helicase DNA binding protein 3 (CHD3) gene. To date, more than 100 individuals have been diagnosed with SNIBCPS. The syndrome is characterized by intellectual disability, global developmental delay, speech or language impediments, and dysmorphic features associated with macrocephaly. Additionally, affected individuals may exhibit behavioral issues, hypotonia, and autistic traits. A novel splicing variant (c.5590+1G > T) in the C-terminal 2 region of the CHD3 gene was identified in a patient predominantly exhibiting autistic characteristics. In vitro minigene splicing experiments conducted in HEK293 cells revealed that aberrant splicing resulted in the formation of a cryptic site 46 nucleotides downstream of the 5' splice site. This alteration was predicted to disrupt the reading frame by eliminating the physiological stop codon, consequently causing an extension in protein translation. Furthermore, an additional patient presenting with hypotonia, dysmorphic features, and global developmental delay was documented. This patient harbored a missense variant in the helicase C-terminal domain, c.3505C > T (p. Arg1169Trp). The pathogenic variant was anticipated to impact chromatin remodeling capacity and enzyme activity. Given the high prevalence of arginine residue pathogenic variants in the CHD3 protein and its notable propensity for binding and storing ATP molecules, intriguing insights into the potential effects of arginine residue pathogenic variants on phenotypes are provided. These findings contribute to a more comprehensive understanding of the genetic landscape of SNIBCPS while elucidating potential molecular mechanisms underlying the syndrome.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63930"},"PeriodicalIF":1.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612208","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