American Journal of Medical Genetics Part A最新文献_第2页

New Insights Into the Spectrum of RASopathies: Clinical and Genetic Data in a Cohort of 121 Spanish Patients. RAS 病谱的新发现：121名西班牙患者的临床和遗传数据。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-01 DOI: 10.1002/ajmg.a.63905

Ana Isabel Sánchez Barbero, Irene Valenzuela, Paula Fernández-Alvarez, Élida Vazquez, Anna Maria Cueto-Gonzalez, Amaia Lasa-Aranzasti, Laura Trujillano, Bárbara Masotto, Elena García Arumí, Eduardo F Tizzano

{"title":"New Insights Into the Spectrum of RASopathies: Clinical and Genetic Data in a Cohort of 121 Spanish Patients.","authors":"Ana Isabel Sánchez Barbero, Irene Valenzuela, Paula Fernández-Alvarez, Élida Vazquez, Anna Maria Cueto-Gonzalez, Amaia Lasa-Aranzasti, Laura Trujillano, Bárbara Masotto, Elena García Arumí, Eduardo F Tizzano","doi":"10.1002/ajmg.a.63905","DOIUrl":"https://doi.org/10.1002/ajmg.a.63905","url":null,"abstract":"Noonan syndrome and related disorders are a group of well-known genetic conditions caused by dysregulation of the Ras/mitogen-activated protein kinase (RAS/MAPK) pathway. Because of the overlap of clinical and molecular features, they are now called RASopathies. In this study, we retrospectively analyzed the clinical data of 121 patients with a molecularly confirmed diagnosis of RASopathy, describing frequencies for clinical features in all organ systems as well as molecular data. The most common clinical diagnosis was Noonan Syndrome and the most frequently affected gene was PTPN11 followed by SOS1, RAF1, LZTR1, and RIT1. All patients had distinctive craniofacial features indicative of the RASopathy spectrum but we report some atypical features regarding craniofacial shape, such as craniosynostosis and microcephaly. We also describe uncommon clinical characteristics such as aortic dilation, multivalvular heart disease, abnormalities of the posterior fossa, and uterine congenital anomalies in female patients. Furthermore, the presence of multiple giant cell granulomas was observed specifically in patients with SOS1 variants. This comprehensive evaluation allows broadening the phenotypic spectrum of our population and their correlation with the genotype, which are essential to improve the recognition and the follow up of RASopathies as a multisystemic disease.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556899","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

CTNND1-Related Disorder: New Insight on Prenatal Phenotype. CTNND1 相关疾病：产前表型的新见解。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-11-01 DOI: 10.1002/ajmg.a.63921

B Conti, C Di Napoli, S Hafdaoui, V Nicotra, C Cesaretti, L Runza, V Accurti, S Boito, M Iascone, D Marchetti, R Silipigni, P Finelli, F Natacci

{"title":"CTNND1-Related Disorder: New Insight on Prenatal Phenotype.","authors":"B Conti, C Di Napoli, S Hafdaoui, V Nicotra, C Cesaretti, L Runza, V Accurti, S Boito, M Iascone, D Marchetti, R Silipigni, P Finelli, F Natacci","doi":"10.1002/ajmg.a.63921","DOIUrl":"https://doi.org/10.1002/ajmg.a.63921","url":null,"abstract":"CTNND1 is a gene located in 11q12.1, encoding for p120 catenin, a protein involved in maintaining adherent junctions, regulating the epithelial-mesenchymal transition, and transcriptional signaling of different cellular pathways. Pathogenic variants in CTNND1 are classically associated with isolated cleft palate and Blefaro-cheilo-dontic syndrome, an autosomal dominant condition characterized by abnormalities of the eyelid. Considering different signs and symptoms associated first with Blefaro-cheilo-dontic syndrome and later specifically with CTNND1, Ahlaratani and colleagues proposed a wider developmental role for CTNND1 than previously described, associating a broader phenotypic spectrum. This report describes a prenatal case in which a CTNND1 pathogenic variant and reverse phenotyping allowed a diagnosis of Blefaro-cheilo-dontic syndrome associated with characteristics never related to Blefaro-cheilo-dontic syndrome or CTNND1, such as hydrocephalus. This report is the first detailed fetal case of Blefaro-cheilo-dontic syndrome, and the new feature reported is consistent with CTNND1 developmental role and may add new insights into the phenotype spectrum that is being defined.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563749","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

Successful Pregnancy Outcome With Preconception Care in a Symptomatic Carrier of Duchenne Muscular Dystrophy: Case Report and Literature Review. 有症状的杜兴氏肌肉萎缩症携带者通过孕前保健成功怀孕：病例报告和文献综述。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-31 DOI: 10.1002/ajmg.a.63926

Motoaki Kinugawa, Mari Ichinose, Haruka Matsui, Zeng Xiang, Seisuke Sayama, Masatake Toshimitsu, Takahiro Seyama, Hitomi Masuda, Hikoro Matsui, Keiichi Kumasawa, Takayuki Iriyama, Yasushi Hirota, Yutaka Osuga

{"title":"Successful Pregnancy Outcome With Preconception Care in a Symptomatic Carrier of Duchenne Muscular Dystrophy: Case Report and Literature Review.","authors":"Motoaki Kinugawa, Mari Ichinose, Haruka Matsui, Zeng Xiang, Seisuke Sayama, Masatake Toshimitsu, Takahiro Seyama, Hitomi Masuda, Hikoro Matsui, Keiichi Kumasawa, Takayuki Iriyama, Yasushi Hirota, Yutaka Osuga","doi":"10.1002/ajmg.a.63926","DOIUrl":"https://doi.org/10.1002/ajmg.a.63926","url":null,"abstract":"Duchenne Muscular Dystrophy (DMD) is an X-linked recessive disorder. Female carriers can manifest symptoms during pregnancy, complicating diagnosis and genetic counseling before conception. This is the first report of a DMD symptomatic carrier who was managed continuously from preconception through pregnancy for symptoms recognized before conception. A 31-year-old primipara woman was incidentally noted to have premature ventricular contractions, heart failure, and elevated creatine kinase levels 2 years before pregnancy. Genetic testing confirmed that the patient was a symptomatic carrier of DMD. She had no family history of muscular or cardiac disease, suggesting a de novo variant. She received genetic counseling and planned amniocentesis during pregnancy as prenatal diagnosis. After treatment with bisoprolol and flecainide, her cardiac function improved, and natural conception was achieved. Amniocentesis performed at 16 weeks of gestation indicated a 46, XX karyotype, leading to the decision to continue the pregnancy. From week 16 to 21, the fetus exhibited bradycardia due to blocked premature atrial contraction, which later improved, although the atrioventricular interval was prolonged. The mother delivered vaginally without any complications, and the infant's atrioventricular interval normalized. Preconceptional diagnosis and treatment for DMD carrier status are crucial for shared decision-making and to achieve favorable perinatal outcomes.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556900","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

ARSA Variant Associated With Late Infantile Metachromatic Leukodystrophy and Carrier Rate in Individuals of Ashkenazi Jewish Ancestry. 与晚期婴幼儿变性白营养不良症相关的 ARSA 变异及阿什肯纳兹犹太血统个体的携带率。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-30 DOI: 10.1002/ajmg.a.63919

Rachel Rabin, Yoel Hirsch, Kevin T A Booth, Patricia L Hall, Naomi Yachelevich, Pramod K Mistry, Josef Ekstein, John Pappas

{"title":"ARSA Variant Associated With Late Infantile Metachromatic Leukodystrophy and Carrier Rate in Individuals of Ashkenazi Jewish Ancestry.","authors":"Rachel Rabin, Yoel Hirsch, Kevin T A Booth, Patricia L Hall, Naomi Yachelevich, Pramod K Mistry, Josef Ekstein, John Pappas","doi":"10.1002/ajmg.a.63919","DOIUrl":"https://doi.org/10.1002/ajmg.a.63919","url":null,"abstract":"Metachromatic leukodystrophy (MLD) is a rare neurodegenerative lysosomal storage disease resulting from bi-allelic pathogenic variants in the ARSA gene. MLD is distinguished clinically based on the age of onset into late-infantile, juvenile, and adult. The late-infantile type is the most severe phenotype presenting with hypotonia, weakness, gait abnormalities, which progresses to mental and physical decline leading to early death. MLD is considered to be pan-ethnic and no founder variants have previously been described in the Ashkenazi Jewish population. We identified three unrelated individuals of Ashkenazi Jewish descent with homozygosity or compound heterozygosity for the c.178C>T (p.Arg60Trp) variant in the ARSA gene, with a phenotype consistent with late-infantile MLD. The carrier frequency was calculated among 93,293 individuals of Ashkenazi Jewish descent through the Dor Yeshorim screening program and found to have a carrier frequency on 1 in 1554 or 0.06%, which may be representative of a founder variant. Molecular protein modeling showed that the variant affects regional folding. Late-infantile MLD should be considered when the c.178C>T (p.Arg60Trp) variant in the ARSA gene is present in either the homozygous or the compound heterozygous states.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543095","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

Neuroimaging to Genotype: Delineating the Spectrum of Disorders With Deficient Myelination in the Indian Population. 从神经成像到基因型：划定印度人群髓鞘缺失症的范围

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-29 DOI: 10.1002/ajmg.a.63914

Namanpreet Kaur, Michelle C do Rosario, Purvi Majethia, Selinda Mascarenhas, Lakshmi Priya Rao, Karthik Vijay Nair, Bhagesh Hunakunti, Adarsh Pooradan Prasannakumar, Rohit Naik, Dhanya Lakshmi Narayanan, Shalini S Nayak, Vivekananda Bhat, Suvasini Sharma, Y Ramesh Bhat, B L Yatheesha, Rajesh Kulkarni, Siddaramappa J Patil, Sheela Nampoothiri, Shahyan Siddiqui, Katta Mohan Girisha, Stephanie Bielas, Anju Shukla

{"title":"Neuroimaging to Genotype: Delineating the Spectrum of Disorders With Deficient Myelination in the Indian Population.","authors":"Namanpreet Kaur, Michelle C do Rosario, Purvi Majethia, Selinda Mascarenhas, Lakshmi Priya Rao, Karthik Vijay Nair, Bhagesh Hunakunti, Adarsh Pooradan Prasannakumar, Rohit Naik, Dhanya Lakshmi Narayanan, Shalini S Nayak, Vivekananda Bhat, Suvasini Sharma, Y Ramesh Bhat, B L Yatheesha, Rajesh Kulkarni, Siddaramappa J Patil, Sheela Nampoothiri, Shahyan Siddiqui, Katta Mohan Girisha, Stephanie Bielas, Anju Shukla","doi":"10.1002/ajmg.a.63914","DOIUrl":"10.1002/ajmg.a.63914","url":null,"abstract":"Several genetic disorders are associated with either a permanent deficit or a delay in central nervous system myelination. We investigated 24 unrelated families (25 individuals) with deficient myelination after clinical and radiological evaluation. A combinatorial approach of targeting and/or genomic testing was employed. Molecular diagnosis was achieved in 22 out of 24 families (92%). Four families (4/9, 44%) were diagnosed with targeted testing and 18 families (18/23, 78%) were diagnosed using broad genomic testing. Overall, 14 monogenic disorders were identified. Twenty disease-causing variants were identified in 14 genes including PLP1, GJC2, POLR1C, TUBB4A, UFM1, NKX6-2, DEGS1, RNASEH2C, HEXA, ATP7A, SETBP1, GRIN2B, OCLN, and ZBTB18. Among these, nine (45%) variants are novel. Fourteen families (82%, 14/17) were diagnosed using proband-only exome sequencing (ES) complemented with deep phenotyping, thus highlighting the utility of singleton ES as a valuable diagnostic tool for identifying these disorders in resource-limited settings.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520713","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

Recurrent Increased Nuchal Translucency Led to the Identification of Novel NUP107 Variants. 反复出现的颈部半透明增加导致新型 NUP107 变异的发现

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-29 DOI: 10.1002/ajmg.a.63920

Isis Atallah, Katarina Cisarova, Cécile Guenot, Estelle Dubruc, Andrea Superti-Furga, Belinda Campos-Xavier, Sheila Unger

{"title":"Recurrent Increased Nuchal Translucency Led to the Identification of Novel NUP107 Variants.","authors":"Isis Atallah, Katarina Cisarova, Cécile Guenot, Estelle Dubruc, Andrea Superti-Furga, Belinda Campos-Xavier, Sheila Unger","doi":"10.1002/ajmg.a.63920","DOIUrl":"https://doi.org/10.1002/ajmg.a.63920","url":null,"abstract":"Five percent of fetuses presents increased fetal nuchal translucency. It is a well-known marker for aneuploidy (T21, Turner syndrome) and a variety of monogenic syndromes such as Noonan syndrome and certain skeletal dysplasias, as well as associated with structural malformations such as congenital heart disease. Current diagnostic algorithms for increased nuchal translucency include a rapid test for aneuploidy (fluorescence in situ hybridization, FISH, or quantitative PCR), a cytogenetic analysis (karyotype or chromosomal microarray, CMA) followed by or concurrent with targeted gene panel analysis for RASopathies/Noonan syndrome. Some centers now propose whole exome sequencing as an adjunct, but its usefulness in isolated increased nuchal translucency remains debated. We describe the recurrence of apparently isolated increased nuchal translucency in 2 euploid fetuses. Whole genome sequencing identified two compound heterozygous variants in the NUP107 gene in both fetuses. Biallelic variants in NUP107 are responsible for severe steroid-resistant nephrotic syndrome, either isolated or syndromic (Galloway-Mowat syndrome); in addition to the renal phenotype, the latter also includes intellectual deficiency and dysmorphic features. Pregnancy termination made it impossible to assess whether the NUP107 variants found would have resulted in isolated or syndromic steroid-resistant nephrotic syndrome. However, identifying the responsible gene improved the accuracy of the genetic counseling. This family is an example of the added benefit of introducing WES/WGS in standardized protocols for prenatal diagnosis of euploid fetuses in \"isolated\" increased nuchal translucency.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543096","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

Further Evidence for a Possible Role for ZHFX4 in Human Ocular Development and Disease. 进一步证明 ZHFX4 在人类眼部发育和疾病中的可能作用

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-25 DOI: 10.1002/ajmg.a.63911

Linda M Reis, Gerald W Zaidman, Samuel Thompson, Sanaa Muheisen, Tom Glaser, Elena V Semina

引用次数: 0

Recurrent Xp22.31-Yq11 Unbalanced Translocations: Molecular Diagnosis and Clinical Implications in Three Families. 复发性 Xp22.31-Yq11 不平衡易位：三个家族的分子诊断和临床意义。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-23 DOI: 10.1002/ajmg.a.63913

Marwa Daghsni, Elizabeth Sheehan, Suneeta Madan-Khetarpal, Mahmoud Aarabi, Selma F Witchel, Aleksandar Rajkovic, Svetlana A Yatsenko

{"title":"Recurrent Xp22.31-Yq11 Unbalanced Translocations: Molecular Diagnosis and Clinical Implications in Three Families.","authors":"Marwa Daghsni, Elizabeth Sheehan, Suneeta Madan-Khetarpal, Mahmoud Aarabi, Selma F Witchel, Aleksandar Rajkovic, Svetlana A Yatsenko","doi":"10.1002/ajmg.a.63913","DOIUrl":"https://doi.org/10.1002/ajmg.a.63913","url":null,"abstract":"Unbalanced translocation between chromosomes X and Y is a recurring chromosomal rearrangement. The presence of a derivative chromosome X (derX), where a Yq11-qter segment is attached to the short arm of chromosome X, replacing a terminal Xpter-p22.31, poses challenges for interpretation of findings by prenatal cell-free DNA (cfDNA) screening, establishing genotype-phenotype correlation in male and female individuals, and for genetic counseling. In this report, we provide clinical outcomes, inheritance, and clinical implications of derX in three families referred to diagnostic testing due to discrepant results for sex chromosomes reported by cfDNA, abnormal prenatal ultrasound findings, recurrent pregnancy losses, or affected family members with derX transmitted through multiple generations. Reports of discrepant sex and risk for sex chromosome aneuploidy such as 45,X, 47,XXY and 47,XYY are common false positive outcomes of a prenatal cfDNA screening if either a mother or a fetus has unbalanced Xp-Yq translocation. In addition, mothers who carry der(X) facing a recurrent risk of ambiguity in prenatal testing. Pregnancy loss and neonatal death/stillbirth of male offspring are common in affected families, but this risk does not directly correlate with the size of deleted Xp region. This study emphasizes the importance of CMA and familial testing for accurate diagnosis and genetic counseling.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492862","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

Expanding the Phenotype of Extremely Early Onset Juvenile Huntington's Disease: A Case Report and Review of Previously Published Cases. 扩展极早发青少年亨廷顿氏病的表型：病例报告和以往发表病例的回顾。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-23 DOI: 10.1002/ajmg.a.63894

Zöe Powis, Jonathon Lutz, Khalida Liaquat, Jyes A Querubin, Sat Dev Batish

引用次数: 0

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-23 DOI: 10.1002/ajmg.a.63912

Michael A Cirelli, Philip Wackel, Rabia Javed, Ralitza Gavrilova, M Yasir Qureshi, Joseph A Dearani, Lauren M Boucher, Talha Niaz

引用次数: 0