Clinical Genetics最新文献_第3页

Second Case of Gonadal Mosaicism and a Novel Nonsense NR2F1 Gene Variant as the Cause of Bosch–Boonstra–Schaaf Optic Atrophy Syndrome 第二例性腺嵌合体和新型无义 NR2F1 基因变异导致的 Bosch-Boonstra-Schaaf 视神经萎缩综合征。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-09-30 DOI: 10.1111/cge.14623

Nenad Hrvatin, Nina Pereza, Tea Čaljkušić-Mance, Tamara Mišljenović Vučerić, Saša Ostojić, Alenka Hodžić, Aleš Maver, Borut Peterlin

{"title":"Second Case of Gonadal Mosaicism and a Novel Nonsense NR2F1 Gene Variant as the Cause of Bosch–Boonstra–Schaaf Optic Atrophy Syndrome","authors":"Nenad Hrvatin, Nina Pereza, Tea Čaljkušić-Mance, Tamara Mišljenović Vučerić, Saša Ostojić, Alenka Hodžić, Aleš Maver, Borut Peterlin","doi":"10.1111/cge.14623","DOIUrl":"10.1111/cge.14623","url":null,"abstract":"<div>\u0000 \u0000 Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is an autosomal dominant disease characterized by developmental delay, intellectual disability, and optic atrophy with a variable expression of other clinical features (dysmorphic features, autistic behaviour, corpus callosum hypoplasia and seizures). To date, approximately a hundred cases of the syndrome have been described, with an estimated prevalence of 1 in 100 000–250 000. BBSOAS is caused by the loss of function of the NR2F1 gene (nuclear receptor subfamily 2 group F member 1), which encodes the COUP-TFI (Chicken ovalbumin upstream promotor-transcription factor 1). COUP-TFI functions as a homodimer and is one of the major transcriptional regulators directing cortical arealization, cell differentiation and maturation. Most cases of BBSOAS occur de novo, and one case was previously described in which the disease resulted from gonadal mosaicism. In the present case, we report two sisters with BBSOAS, a novel nonsense mutation in the NR2F1 gene and potential gonadal mosaicism as the cause of this rare disease, making it the second such case described in the literature.\u0000 </div>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Review of susceptibility genes in developmental dysplasia of the hip: A comprehensive examination of candidate genes and pathways. 髋关节发育不良易感基因综述：候选基因和途径的全面审查。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-09-22 DOI: 10.1111/cge.14618

Wenla Wang, Wei Zhuang, Wenxiang Zeng, Yuqi Feng, Zhaowei Zhang

{"title":"Review of susceptibility genes in developmental dysplasia of the hip: A comprehensive examination of candidate genes and pathways.","authors":"Wenla Wang, Wei Zhuang, Wenxiang Zeng, Yuqi Feng, Zhaowei Zhang","doi":"10.1111/cge.14618","DOIUrl":"https://doi.org/10.1111/cge.14618","url":null,"abstract":"Developmental dysplasia of the hip (DDH) is one of the most prevalent skeletal deformities, primarily due to the incompatibility between the acetabulum and femoral head. It includes complete dislocation, partial dislocation, instability with femoral head subluxation, and a range of imaging abnormalities that reflect inadequate acetabular formation. Known risk factors for DDH include positive family history, sex, premature birth, non-cephalic delivery, oligohydramnios, gestational diabetes mellitus, maternal hypertension, associated anomalies, swaddling clothes, intrauterine space restriction, and post-term pregnancy. Various research designs have been employed in DDH studies to identify relevant genes, including candidate gene association studies (CGAS), genome-wide association studies (GWAS), restriction fragment length polymorphism (RFLP), and whole exome sequencing (WES). To date, multiple DDH-associated genes have been identified in various populations. Despite extensive research into the epidemiology, risk factors, and genes associated with DDH, its pathogenesis remains unclear. This study provides a comprehensive summary of DDH research designs and evidence for relevant gene mutations through a PubMed search.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel KIF26A variants associated with pediatric intestinal pseudo-obstruction (PIPO) and brain developmental defects. 与小儿肠道假性梗阻（PIPO）和大脑发育缺陷有关的新型 KIF26A 变异。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-09-21 DOI: 10.1111/cge.14621

Mohammad Sadegh Shams Nosrati, Alireza Doustmohammadi, Mariasavina Severino, Ferruccio Romano, Mahdi Zafari, Amir Hesam Nemati, Clara Velmans, Christian Netzer, Jonas Breuer, Ilse Julia Broekaert, Alexander Joachim, Nihad Almasri, Michael C Kruer, Peter Skidmore, Pritha Bisarad, Jumana Hoque, Somayeh Bakhtiari, Annalaura Torella, Vincenzo Nigro, Francesca Buffelli, Ezio Fulcheri, Annette Müller, Federico Zara, Valeria Capra, Marcello Scala

{"title":"Novel KIF26A variants associated with pediatric intestinal pseudo-obstruction (PIPO) and brain developmental defects.","authors":"Mohammad Sadegh Shams Nosrati, Alireza Doustmohammadi, Mariasavina Severino, Ferruccio Romano, Mahdi Zafari, Amir Hesam Nemati, Clara Velmans, Christian Netzer, Jonas Breuer, Ilse Julia Broekaert, Alexander Joachim, Nihad Almasri, Michael C Kruer, Peter Skidmore, Pritha Bisarad, Jumana Hoque, Somayeh Bakhtiari, Annalaura Torella, Vincenzo Nigro, Francesca Buffelli, Ezio Fulcheri, Annette Müller, Federico Zara, Valeria Capra, Marcello Scala","doi":"10.1111/cge.14621","DOIUrl":"https://doi.org/10.1111/cge.14621","url":null,"abstract":"Pediatric intestinal pseudo-obstruction (PIPO) is a rare congenital disorder of the enteric nervous system with distal colon aganglionosis potentially leading to intestinal obstruction. Recently, biallelic variants in KIF26A, encoding a crucial motor protein for the migration and differentiation of enteric neural crest cells, have been associated with a neurodevelopmental condition featuring cortical defects and PIPO-like features, though in absence of aganglionosis. So far, only 10 patients have been reported. In this study, we investigated three subjects with congenital hydrocephalus, neurodevelopmental impairment, and intestinal obstruction megacolon syndrome. Brain MRI revealed malformations within cortical dysplasia spectrum, including polymicrogyria and heterotopia. Pathology study of the intestine revealed aganglionosis and elevated acetylcholinesterase activity in parasympathetic nerve fibers. Through trio-exome sequencing (ES), we detected four novel biallelic KIF26A variants, including two missense changes (#1) and two distinct homozygous truncating variants in (#2 and #3). All variants are rare and predicted to be deleterious according to in silico tools. To characterize the impact of the missense variants, we performed 3D protein modeling using Alphafold3 and YASARA. Mutants exhibited increased energy scores compared to wild-type protein, supporting a significant structural destabilization of the protein. Our study expands the genotype and phenotype spectrum of the emerging KIF26A-related disorder.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Research progress of the relationship between phosphoprotein phosphatases (PPPs) and neurodevelopmental disorders 磷蛋白磷酸酶（PPPs）与神经发育障碍之间关系的研究进展。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-09-19 DOI: 10.1111/cge.14617

Wenya Ji, Bixia Zheng, Aihua Zhang

{"title":"Research progress of the relationship between phosphoprotein phosphatases (PPPs) and neurodevelopmental disorders","authors":"Wenya Ji, Bixia Zheng, Aihua Zhang","doi":"10.1111/cge.14617","DOIUrl":"10.1111/cge.14617","url":null,"abstract":"Reversible protein phosphorylation is a ubiquitous phenomenon essential for eukaryotic cellular processes. Recent advancements in research about neurodevelopmental disorders have prompted investigations into the intricate relationship between protein phosphatases, particularly phosphoprotein phosphatases (PPPs), and neurodevelopment. Notably, variants in 10 coding genes spanning four PPP family members have been implicated in neurodevelopmental disorders. Here, we provide a comprehensive overview of the clinical phenotypes, genotypes, and pathogenic mechanisms observed in affected patients. Our analysis reveals challenges in subsequent statistical analyses due to inconsistent clinical phenotypic descriptions and a lack of large multicenter studies, hampering analysis about genotype–phenotype correlations. The scarcity of follow-up data poses a significant obstacle to prognostic counseling for nearly all rare diseases. Presently, symptomatic treatment strategies are employed for patients with variants, as definitive cures remain elusive. Future research may explore protein phosphatase regulators as potential therapeutic targets. Furthermore, it is imperative not to overlook other members of the protein phosphatase family or coding genes with undiscovered variants. Insights gleaned from the temporal and spatial distribution of proteins, along with observations from animal model phenotypes, may provide valuable directions for uncovering novel pathogenic genes.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Knowledge and perceptions about fragile X syndrome and fragile X-premutation-associated conditions among medical doctors in Nigeria. 尼日利亚医生对脆性 X 综合征和脆性 X 突变相关疾病的了解和看法。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-09-18 DOI: 10.1111/cge.14619

Chioma N P Mbachu, Randi Hagerman, Edwin Eseigbe, Amalachukwu Odita, Ikechukwu Mbachu, Samuel Ilikanu, Kasarachi Akowundu, Chizalu Ndukwu, Malachy Echezona, Onyedikachi Okereke, Sylvia Echendu, Ifeoma Udigwe

{"title":"Knowledge and perceptions about fragile X syndrome and fragile X-premutation-associated conditions among medical doctors in Nigeria.","authors":"Chioma N P Mbachu, Randi Hagerman, Edwin Eseigbe, Amalachukwu Odita, Ikechukwu Mbachu, Samuel Ilikanu, Kasarachi Akowundu, Chizalu Ndukwu, Malachy Echezona, Onyedikachi Okereke, Sylvia Echendu, Ifeoma Udigwe","doi":"10.1111/cge.14619","DOIUrl":"https://doi.org/10.1111/cge.14619","url":null,"abstract":"Fragile X syndrome (FXS) is a significant cause of intellectual disability and autism, while Fragile X Premutation -Associated Conditions (FXPAC) are a significant cause of morbidity and mortality globally. This study assessed the level of knowledge and perceptions about FXS and FXPAC among doctors in Nigeria. It was a web-based, cross-sectional study conducted among a cohort of doctors in Nigeria. Socio-demographic profile, knowledge of FXS, perceptions about FXS, knowledge of FXPAC, experience of doctors, and suggested ways of improving knowledge and management of FXS were obtained. Data were analyzed using STATA 16.0. Chi-square and Fisher's exact tests of association were used to determine the association between variables, with the significance level set at p < 0.05. A total of 274 doctors participated in the study. A significant proportion of respondents had limited knowledge about the clinical features of FXS. Nine of ten (90.0%) participants with good knowledge of FXS had good perceptions of FXS management. This was statistically significant (p < 0.001). There was a high nonresponse rate to what FXPAC is (164/274, 59.9%) among the respondents because of insufficient knowledge. Suboptimal knowledge of FXS which influenced perception was noted among doctors. More strategies should be considered to improve doctors' knowledge and management of FXS and FXPAC in Nigeria.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetics of anomalies of the kidney and urinary tract with congenital heart disease: A review 肾脏和泌尿道异常与先天性心脏病的遗传：综述。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-09-17 DOI: 10.1111/cge.14615

Amin J. Barakat, Merlin G. Butler

{"title":"Genetics of anomalies of the kidney and urinary tract with congenital heart disease: A review","authors":"Amin J. Barakat, Merlin G. Butler","doi":"10.1111/cge.14615","DOIUrl":"10.1111/cge.14615","url":null,"abstract":"Congenital anomalies of the kidney and urinary tract (CAKUT) and congenital heart disease (CHD) are the most common congenital defects and constitute a major cause of morbidity in children. Anomalies of both systems may be isolated or associated with congenital anomalies of other organ systems. Various reports support the co-occurrence of CAKUT and CHD, although the prevalence can vary. Cardiovascular anomalies occur in 11.2% to 34% of patients with CAKUT, and CAKUT occur in 5.3% to 35.8% of those with CHD. The co-occurrence of genetic factors in both CAKUT and CHD would raise common etiologies including genetics, genetic-environmental interactions, or shared molecular mechanisms and pathways such as NODAL, NOTCH, BMP, WNT, and VEGF. Studies in animal models and humans have indicated a genetic etiology for CHD and CAKUT with hundreds of genes recognized and thousands of entries, found in a catalog of human genetic disorders. There are over 80 CAKUT genes and over 100 CHD genes available for clinical testing. For example, the HNFIB gene accounts for 5% to 31% of reported cases of CAKUT. In view of the association between CAKUT and CHD, a thorough cardiac examination should be performed in patients with CAKUT, and a similar evaluation for CAKUT in the presence of CHD. This will allow early diagnosis and therapeutic intervention to improve the long- term outcome of patients affected, and test for at-risk family members. We present here evidence for an association of anomalies involving the two organ systems, and discuss possible etiologies of targeted genes, their functions, biological processes and interactions on embryogenesis.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14615","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect. 人类骨骼发育不良伴房室间隔缺损中 BMP5 两个变体的复合杂合性。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-09-06 DOI: 10.1111/cge.14616

Pernille Axél Gregersen, Anna Hammarsjö, Lise Graversen, Nis Brix, Hillevi Lindelöf, Uffe Birk Jensen, Stense Farholt, Sune Rubak, Jesper Bjerre, Serena G Piticchio, Thorkild Terkelsen, Gen Nishimura, Michel Bach Hellfritzsch, Giedre Grigelioniene

引用次数: 0

Multiple congenital anomalies in two fetuses with glutathione-synthetase deficit (GSS) 两个谷胱甘肽合成酶缺乏症（GSS）胎儿的多种先天性畸形。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-09-02 DOI: 10.1111/cge.14613

Jeanne Jury, Jean-François Benoist, Madeleine Joubert, Chloé Quelin, Thomas Besnard, Solène Conrad, Claudine Le Vaillant, Stéphane Bézieau, Bertrand Isidor, Tania Attié-Bitach, Benjamin Cogné, Marie Vincent

{"title":"Multiple congenital anomalies in two fetuses with glutathione-synthetase deficit (GSS)","authors":"Jeanne Jury, Jean-François Benoist, Madeleine Joubert, Chloé Quelin, Thomas Besnard, Solène Conrad, Claudine Le Vaillant, Stéphane Bézieau, Bertrand Isidor, Tania Attié-Bitach, Benjamin Cogné, Marie Vincent","doi":"10.1111/cge.14613","DOIUrl":"10.1111/cge.14613","url":null,"abstract":"Glutathione synthetase deficiency is a rare inborn metabolic disease usually caused by biallelic variants in GSS. Clinical severity varies from isolated hemolytic anemia, sometimes associated with chronic metabolic acidosis and 5-oxoprolinuria, to severe neurological phenotypes with neonatal lethality. Here we report on two fetal siblings from two pregnancies with glutathione synthetase deficiency exhibiting similar multiple congenital anomalies associating phocomelia, cleft palate, intra-uterine growth retardation, genito-urinary malformations, and congenital heart defect. Genome sequencing showed that both fetuses were compound heterozygous for two GSS variants: the previously reported pathogenic missense substitution NM_000178.4 c.800G>A p.(Arg267Gln), and a 2.4 kb intragenic deletion NC_000020.11:g.34944530_34946833del. RNA-seq on brain tissue revealed the out-of-frame deletion of the exon 3 and an almost monoallelic expression of the missense variant (88%), suggesting degradation of the deletion-harboring allele by nonsense-mediated mRNA decay. 5-oxoproline (pyroglutamic acid) levels in amniotic fluid were elevated, suggesting an alteration of the gamma-glutamyl cycle, and corroborating the pathogenicity of the two GSS variants. Only one case of glutathione synthetase deficiency with limb malformations has previously been reported, in a newborn homozygous for the c.800G>A variant. Thus, our data allow us to discuss a potential phenotypic extension of glutathione synthetase deficiency, with a possible involvement of the c.800G>A variant.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14613","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dissecting CASK: Novel splice site variant associated with male MICPCH phenotype 剖析 CASK：与男性 MICPCH 表型相关的新剪接位点变异

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-30 DOI: 10.1111/cge.14610

Karina C. Silveira, Anastasia Ambrose, Taryn Athey, Sherryl Taylor, Saadet Mercimek-Andrews, Peter Kannu

{"title":"Dissecting CASK: Novel splice site variant associated with male MICPCH phenotype","authors":"Karina C. Silveira, Anastasia Ambrose, Taryn Athey, Sherryl Taylor, Saadet Mercimek-Andrews, Peter Kannu","doi":"10.1111/cge.14610","DOIUrl":"10.1111/cge.14610","url":null,"abstract":"CASK (MIM#300172), encoding a calcium/calmodulin-dependent serine protein kinase, is crucial for synaptic transmission and gene regulation during neural development. Pathogenic variants of CASK are known to cause several neurodevelopmental disorders, including X-linked intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH). This study introduces a novel, de novo synonymous CASK variant (NM_001367721.1: c.1737G>A, p.(Glu579=)), discovered in a male patient diagnosed with MICPCH, characterized by microcephaly, developmental delay, visual impairment, and myoclonic seizures. The variant disrupts a donor splice-site at the end of exon 18. Transcriptomic analysis of blood identified 12 different CASK transcripts secondary to the synonymous variant. Nearly one third of these transcripts were predicted to result in nonsense mediated decay or protein degradation. Protein modeling revealed structural alterations in the PDZ functional domain of CASK, due to exon 18 deletion. Our findings highlight the utility of transcriptomic analysis in demonstrating the underlying disease mechanism in neurodevelopmental disorders.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Childhood glaucoma: Implications for genetic counselling 儿童青光眼：遗传咨询的意义。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-08-29 DOI: 10.1111/cge.14603

Giorgina Maxwell, Emmanuelle Souzeau

引用次数: 0