Clinical Genetics最新文献_第8页

A homozygous ARMC3 splicing variant causes asthenozoospermia and flagellar disorganization in a consanguineous family 同卵 ARMC3 剪接变异导致一个近亲家族出现无精子症和鞭毛紊乱症

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-06-21 DOI: 10.1111/cge.14575

Fazal Rahim, Liu Tao, Khalid Khan, Imtiaz Ali, Aurang Zeb, Ihsan Khan, Sobia Dil, Tanveer Abbas, Ansar Hussain, Muhammad Zubair, Huan Zhang, Ma Hui, Muzammil Ahmad Khan, Wasim Shah, Qinghua Shi

{"title":"A homozygous ARMC3 splicing variant causes asthenozoospermia and flagellar disorganization in a consanguineous family","authors":"Fazal Rahim, Liu Tao, Khalid Khan, Imtiaz Ali, Aurang Zeb, Ihsan Khan, Sobia Dil, Tanveer Abbas, Ansar Hussain, Muhammad Zubair, Huan Zhang, Ma Hui, Muzammil Ahmad Khan, Wasim Shah, Qinghua Shi","doi":"10.1111/cge.14575","DOIUrl":"10.1111/cge.14575","url":null,"abstract":"Male infertility due to asthenozoospermia is quite frequent, but its etiology is poorly understood. We recruited two infertile brothers, born to first-cousin parents from Pakistan, displaying idiopathic asthenozoospermia with mild stuttering disorder but no ciliary-related symptoms. Whole-exome sequencing identified a splicing variant (c.916+1G>A) in ARMC3, recessively co-segregating with asthenozoospermia in the family. The ARMC3 protein is evolutionarily highly conserved and is mostly expressed in the brain and testicular tissue of human. The ARMC3 splicing mutation leads to the exclusion of exon 8, resulting in a predicted truncated protein (p.Glu245_Asp305delfs*16). Quantitative real-time PCR revealed a significant decrease at mRNA level for ARMC3 and Western blot analysis did not detect ARMC3 protein in the patient's sperm. Individuals homozygous for the ARMC3 splicing variant displayed reduced sperm motility with frequent morphological abnormalities of sperm flagella. Transmission electron microscopy of the affected individual IV: 2 revealed vacuolation in sperm mitochondria at the midpiece and disrupted flagellar ultrastructure in the principal and end piece. Altogether, our results indicate that this novel homozygous ARMC3 splicing mutation destabilizes sperm flagella and leads to asthenozoospermia in our patients, providing a novel marker for genetic counseling and diagnosis of male infertility.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 4","pages":"437-447"},"PeriodicalIF":2.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141508255","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

New kinase-deficient PAK2 variants associated with Knobloch syndrome type 2 与 Knobloch 综合征 2 型有关的新型激酶缺陷 PAK2 变体。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-06-18 DOI: 10.1111/cge.14578

Rhonda E. Schnur, Lukáš Dvořáček, Louisa Kalsner, Faye L. Shapiro, Dana Grebeňová, Diana Yanni, Barry N. Wasserman, VIGOR, Lisa M. Dyer, Stylianos E. Antonarakis, Kateřina Kuželová

引用次数: 0

Unraveling GRIA1 neurodevelopmental disorders: Lessons learned from the p.(Ala636Thr) variant 揭示 GRIA1 神经发育障碍：p.(Ala636Thr)变异的教训。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-06-18 DOI: 10.1111/cge.14577

Nicolai Kohring Tvergaard, Tinatin Tkemaladze, Tommy Stödberg, Malin Kvarnung, Katrina Tatton-Brown, Diana Baralle, Zeynep Tümer, Allan Bayat

{"title":"Unraveling GRIA1 neurodevelopmental disorders: Lessons learned from the p.(Ala636Thr) variant","authors":"Nicolai Kohring Tvergaard, Tinatin Tkemaladze, Tommy Stödberg, Malin Kvarnung, Katrina Tatton-Brown, Diana Baralle, Zeynep Tümer, Allan Bayat","doi":"10.1111/cge.14577","DOIUrl":"10.1111/cge.14577","url":null,"abstract":"Ionotropic glutamate receptors (iGluRs), specifically α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), play a crucial role in orchestrating excitatory neurotransmission in the brain. AMPARs are intricate assemblies of subunits encoded by four paralogous genes: GRIA1-4. Functional studies have established that rare GRIA variants can alter AMPAR currents leading to a loss- or gain-of-function. Patients affected by rare heterozygous GRIA variants tend to have family specific variants and only few recurrent variants have been reported. We deep-phenotyped a cohort comprising eight unrelated children and adults, harboring a recurrent and well-established disease-causing GRIA1 variant (NM_001114183.1: c.1906G>A, p.(Ala636Thr)). Recurrent symptoms included motor and/or language delay, mild–severe intellectual disability, behavioral and psychiatric comorbidities, hypotonia and epilepsy. We also report challenges in social skills, autonomy, living and work situation, and occupational levels. Furthermore, we compared their clinical manifestations in relation to those documented in patients presenting with rare heterozygous variants at analogous positions within paralogous genes. This study provides unprecedented details on the neurodevelopmental outcomes, cognitive abilities, seizure profiles, and behavioral abnormalities associated with p.(Ala636Thr) refining and broadening the clinical phenotype.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 4","pages":"427-436"},"PeriodicalIF":2.9,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14577","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418187","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

EZH2-associated tumor malignancy: A prominent target for cancer treatment 与 EZH2 相关的肿瘤恶性程度：癌症治疗的重要靶点

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-06-17 DOI: 10.1111/cge.14576

Maryam Sabour-Takanlou, Leila Sabour-Takanlou, Cigir Biray-Avci

{"title":"EZH2-associated tumor malignancy: A prominent target for cancer treatment","authors":"Maryam Sabour-Takanlou, Leila Sabour-Takanlou, Cigir Biray-Avci","doi":"10.1111/cge.14576","DOIUrl":"10.1111/cge.14576","url":null,"abstract":"The discussion in this review centers around the significant relationships between EZH2 and the initiation, progression, metastasis, metabolism, drug resistance, and immune regulation of cancer. Polycomb group (PcG) proteins, which encompass two primary Polycomb repressor complexes (PRC1 and PRC2), have been categorized. PRC2 consists mainly of four subunits, namely EZH2, EED, SUZ12, and RbAp46/48. As the crucial catalytic component within the PRC2 complex, EZH2 plays a pivotal role in controlling a wide range of biological processes. Overexpression/mutations of EZH2 have been detected in a wide variety of tumors. Several mechanisms of EZH regulation have been identified, including regulation EZH2 mRNA by miRNAs, LncRNAs, accessibility to DNA via DNA-binding proteins, post-translational modifications, and transcriptional regulation. EZH2 signaling triggers cancer progression and may intervene with anti-tumor immunity; therefore it has charmed attention as an effective therapeutic target in cancer therapy. Numerous nucleic acid-based therapies have been used in the modification of EZH2. In addition to gene therapy approaches, pharmaceutical compounds can be used to target the EZH2 signaling pathway in the treatment of cancer. EZH2-associated tumor cells and immune cells enhance the effects of the immune response in a variety of human malignancies. The combination of epigenetic modifying agents, such as anti-EZH2 compounds with immunotherapy, could potentially be efficacious even in the context of immunosuppressive tumors. Summary, understanding the mechanisms underlying resistance to EZH2 inhibitors may facilitate the development of novel drugs to prevent or treat relapse in treated patients.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 4","pages":"377-385"},"PeriodicalIF":2.9,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14576","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330505","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

Short stature and dysmorphic features in Asian Indian siblings with DAAM2-associated steroid-resistant nephrotic syndrome: Expansion of the phenotypic spectrum or a blended phenotype? 患有DAAM2-相关类固醇耐受性肾病综合征的亚裔印度兄弟姐妹身材矮小且畸形：表型谱的扩展还是混合表型？

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-06-11 DOI: 10.1111/cge.14565

T. Pragna Lakshmi, Neelam Saini, Mehul A. Shah, Swarnalata Gowrishankar, Ashwin Dalal, Prajnya Ranganath

{"title":"Short stature and dysmorphic features in Asian Indian siblings with DAAM2-associated steroid-resistant nephrotic syndrome: Expansion of the phenotypic spectrum or a blended phenotype?","authors":"T. Pragna Lakshmi, Neelam Saini, Mehul A. Shah, Swarnalata Gowrishankar, Ashwin Dalal, Prajnya Ranganath","doi":"10.1111/cge.14565","DOIUrl":"10.1111/cge.14565","url":null,"abstract":"Variants in more than 60 different genes, most of which code for podocyte-related proteins, have been found to be associated with monogenic forms of nephrotic syndrome (NS). Biallelic variants in DAAM2, a member of the formin family, were recently identified to cause autosomal recessive (AR) NS type 24 in four unrelated families with steroid-resistant nephrotic syndrome (SRNS). This case report represents only the fifth reported family of DAAM2-associated NS and the first from India, with two sibs who presented with a complex phenotype characterized by steroid-resistant nephrotic syndrome, short stature, dysmorphic facial features, deep-set toenails, myopia, increased thickness of the calvarium of the skull, and sloping ribs. Both sibs were found to have a homozygous likely pathogenic nonsense variant c.196C>T (p.Arg66Ter; NM_001201427.2) in exon 3 of the DAAM2 gene through whole exome sequencing. The dysmorphic features could possibly be part of the DAAM2-related phenotype which has hitherto not been reported or could represent a blended phenotype, with the extrarenal manifestations resulting from a yet to be identified coexisting genetic condition.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 4","pages":"494-499"},"PeriodicalIF":2.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300140","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

Non-syndromic retinal dystrophy associated with biallelic variation of SUMF1 and reduced leukocyte sulfatase activity 与 SUMF1 双偶联变异和白细胞硫酸酯酶活性降低有关的非综合征视网膜营养不良症。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-06-11 DOI: 10.1111/cge.14573

Siying Lin, Anthony G. Robson, Dorothy A. Thompson, Karolina M. Stepien, Robin Lachmann, Emma Footitt, Ola Czyz, Shwetha Chandrasekhar, Elena Schiff, Christos Iosifidis, Graeme C. Black, Michel Michaelides, Omar A. Mahroo, Gavin Arno, Andrew R. Webster

{"title":"Non-syndromic retinal dystrophy associated with biallelic variation of SUMF1 and reduced leukocyte sulfatase activity","authors":"Siying Lin, Anthony G. Robson, Dorothy A. Thompson, Karolina M. Stepien, Robin Lachmann, Emma Footitt, Ola Czyz, Shwetha Chandrasekhar, Elena Schiff, Christos Iosifidis, Graeme C. Black, Michel Michaelides, Omar A. Mahroo, Gavin Arno, Andrew R. Webster","doi":"10.1111/cge.14573","DOIUrl":"10.1111/cge.14573","url":null,"abstract":"Biallelic variants in SUMF1 are associated with multiple sulfatase deficiency (MSD), a rare lysosomal storage disorder typically diagnosed in early infancy or childhood, marked by severe neurodegeneration and early mortality. We present clinical and molecular characterisation of three unrelated patients aged 13 to 58 years with milder clinical manifestations due to SUMF1 disease variants, including two adult patients presenting with apparent non-syndromic retinal dystrophy. Whole genome sequencing identified biallelic SUMF1 variants in all three patients; Patient 1 homozygous for a complex allele c.[290G>T;293T>A]; p.[(Gly97Val);(Val98Glu)], Patient 2 homozygous for c.866A>G; p.(Tyr289Cys), and Patient 3 compound heterozygous for c.726-1G>C and p.(Tyr289Cys). Electroretinography indicated a rod-cone dystrophy with additional possible inner retinal dysfunction in all three patients. Biochemical studies confirmed reduced, but not absent, sulfatase enzyme activity in the absence of extra-ocular disease (Patient 1) or only mild systemic disease (Patients 2, 3). These cases are suggestive that non-null SUMF1 genotypes can cause an attenuated clinical phenotype, including retinal dystrophy without systemic complications, in adulthood.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 4","pages":"505-511"},"PeriodicalIF":2.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14573","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305590","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

Non-dilated left ventricular cardiomyopathy with arrhythmias is commonly caused by the nonsense variant DSP:c.3793G>T in Slovenian patients 在斯洛文尼亚患者中，伴有心律失常的非扩张型左心室心肌病通常是由无义变体 DSP:c.3793G>T 引起的。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-06-11 DOI: 10.1111/cge.14567

Nina Vodnjov, Anja Zupan Mežnar, Aleš Maver, Ajda Dolinšek, Borut Peterlin, Karin Writzl

{"title":"Non-dilated left ventricular cardiomyopathy with arrhythmias is commonly caused by the nonsense variant DSP:c.3793G>T in Slovenian patients","authors":"Nina Vodnjov, Anja Zupan Mežnar, Aleš Maver, Ajda Dolinšek, Borut Peterlin, Karin Writzl","doi":"10.1111/cge.14567","DOIUrl":"10.1111/cge.14567","url":null,"abstract":"DSP-cardiomyopathy has recently been recognised as a specific type of cardiomyopathy. Using an in-house Mendelian disease registry, we aimed to identify probands with likely pathogenic or pathogenic DSP variants. We detected these variants in 4.8% and 77.8% of genotype-positive probands referred for dilated and non-dilated left ventricular cardiomyopathy (NDLVC), respectively. We identified six Slovenian probands with the DSP:c.3793G>T and characterised them along with further eight of their relatives at the molecular and phenotypic level. Medical records revealed NDLVC with arrhythmia in six individuals (five probands, one relative; 33 ± 14 years; three males, three females). All had subepicardial late gadolinium enhancement on cardiac MRI (CMRI), and five received an ICD. Four individuals (one proband, three relatives; 48 ± 14 years; all female) had no ECG and/or cardiac abnormalities on CMRI detected. Our analysis presents a Slovenian-specific molecular pathology of DSP cardiomyopathy, delineates the clinical manifestation of DSP:c.3793C>T, and thereby improves the understanding of the clinical outcomes associated with truncating DSP variants.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 4","pages":"500-504"},"PeriodicalIF":2.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14567","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300138","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

Re-analysis of whole genome sequencing ends a diagnostic odyssey: Case report of an RNU4-2 related neurodevelopmental disorder 全基因组测序的再分析结束了诊断奥德赛：与 RNU4-2 相关的神经发育障碍病例报告。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-06-11 DOI: 10.1111/cge.14574

Rachel Schot, Federico Ferraro, Geert Geeven, Karin E. M. Diderich, Tahsin Stefan Barakat

{"title":"Re-analysis of whole genome sequencing ends a diagnostic odyssey: Case report of an RNU4-2 related neurodevelopmental disorder","authors":"Rachel Schot, Federico Ferraro, Geert Geeven, Karin E. M. Diderich, Tahsin Stefan Barakat","doi":"10.1111/cge.14574","DOIUrl":"10.1111/cge.14574","url":null,"abstract":"Despite increasing knowledge of disease-causing genes in human genetics, approximately half of the individuals affected by neurodevelopmental disorders remain genetically undiagnosed. Part of this missing heritability might be caused by genetic variants outside of protein-coding genes, which are not routinely diagnostically investigated. A recent preprint identified de novo variants in the non-coding spliceosomal snRNA gene RNU4-2 as a cause of a frequent novel syndromic neurodevelopmental disorder. Here we mined 164 whole genome sequencing (WGS) trios from individuals with neurodevelopmental or multiple congenital anomaly disorders that received diagnostic genomic investigations at our clinic. We identify a recurrent de novo RNU4-2 variant (NR_003137.2(RNU4-2):n.64_65insT) in a 5-year-old girl with severe global developmental delay, hypotonia, microcephaly, and seizures that likely explains her phenotype, given that extensive previous genetic investigations failed to identify an alternative cause. We present detailed phenotyping of the individual obtained during a 5-year follow-up. This includes photographs showing recognizable facial features for this novel disorder, which might allow prioritizing other currently unexplained affected individuals sharing similar facial features for targeted investigations of RNU4-2. This case illustrates the power of re-analysis to solve previously unexplained cases even when a diagnostic genome remains negative.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 4","pages":"512-517"},"PeriodicalIF":2.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14574","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300139","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

Expanding the spectrum of phenotypes for MPDZ: Report of four unrelated families and review of the literature 扩大 MPDZ 的表型范围：四个无关家族的报告和文献综述。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-06-10 DOI: 10.1111/cge.14563

Aboulfazl Rad, Oliver Bartsch, Somayeh Bakhtiari, Changlian Zhu, Yiran Xu, Fabíola P. Monteiro, Fernando Kok, Anneke T. Vulto-van Silfhout, Michael C. Kruer, Michael R. Bowl, Barbara Vona

{"title":"Expanding the spectrum of phenotypes for MPDZ: Report of four unrelated families and review of the literature","authors":"Aboulfazl Rad, Oliver Bartsch, Somayeh Bakhtiari, Changlian Zhu, Yiran Xu, Fabíola P. Monteiro, Fernando Kok, Anneke T. Vulto-van Silfhout, Michael C. Kruer, Michael R. Bowl, Barbara Vona","doi":"10.1111/cge.14563","DOIUrl":"10.1111/cge.14563","url":null,"abstract":"MPDZ, a gene with diverse functions mediating cell–cell junction interactions, receptor signaling, and binding multivalent scaffold proteins, is associated with a spectrum of clinically heterogeneous phenotypes with biallelic perturbation. Despite its clinical relevance, the mechanistic underpinnings of these variants remain elusive, underscoring the need for extensive case series and functional investigations. In this study, we conducted a systematic review of cases in the literature through two electronic databases following the PRISMA guidelines. We selected nine studies, including 18 patients, with homozygous or compound heterozygous variants in MPDZ and added five patients from four unrelated families with novel MPDZ variants. To evaluate the role of Mpdz on hearing, we analyzed available auditory electrophysiology data from a knockout murine model (Mpdzem1(IMPC)J/em1(IMPC)J) generated by the International Mouse Phenotyping Consortium. Using exome and genome sequencing, we identified three families with compound heterozygous variants, and one family with a homozygous frameshift variant. MPDZ-related disease is clinically heterogenous with hydrocephaly, vision impairment, hearing impairment and cardiovascular disease occurring most frequently. Additionally, we describe two unrelated patients with spasticity, expanding the phenotypic spectrum. Our murine analysis of the Mpdzem1(IMPC)J/em1(IMPC)J allele showed severe hearing impairment. Overall, we expand understanding of MPDZ-related phenotypes and highlight hearing impairment and spasticity among the heterogeneous phenotypes.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 4","pages":"413-426"},"PeriodicalIF":2.9,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14563","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300137","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

A novel homozygous FAM92A gene (CIBAR1) variant further confirms its association with non-syndromic postaxial polydactyly type A9 (PAPA9) 一个新的同基因 FAM92A 基因（CIBAR1）变异进一步证实了它与非综合征性轴后多指畸形 A9 型（PAPA9）的关联。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-06-10 DOI: 10.1111/cge.14572

Muhammad Umair, Zaheer Ahmed, Bilal Shaker, Muhammad Bilal, Abdulkareem Al Abdulrahman, Hammal Khan, Muhammad Jawad Khan, Majid Alfadhel

{"title":"A novel homozygous FAM92A gene (CIBAR1) variant further confirms its association with non-syndromic postaxial polydactyly type A9 (PAPA9)","authors":"Muhammad Umair, Zaheer Ahmed, Bilal Shaker, Muhammad Bilal, Abdulkareem Al Abdulrahman, Hammal Khan, Muhammad Jawad Khan, Majid Alfadhel","doi":"10.1111/cge.14572","DOIUrl":"10.1111/cge.14572","url":null,"abstract":"Polydactyly is a very common digit anomaly, having extra digits in hands and/or toes. Non-syndromic polydactyly in both autosomal dominant and autosomal recessive forms are caused by disease-causing variants in several genes, including GLI1, GLI3, ZNF141, FAM92A, IQCE, KIAA0825, MIPOL1, STKLD1, PITX1, and DACH1. Whole exome sequencing (WES) followed by bi-directional Sanger sequencing was performed for the single affected individual (II-1) of the family to reveal the disease causative variant/gene. 3D protein modeling and structural molecular docking was performed to determine the effect of the identified mutation on the overall protein structure. WES revealed a novel biallelic missense variant (c.472G>C; p.Ala158Pro) in exon 6 of the FAM92A gene. The identified variant segregated perfectly with the disease phenotype using Sanger sequencing. Furthermore, Insilco analysis revealed that the variant significantly changes the protein secondary structure, and substantially impact the stability of FAM92A. We report the second FAM92A disease-causing mutation associated with recessive non-syndromic postaxial polydactyly. The data further confirms the contribution of FAM92A in limb development and patterning.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"106 4","pages":"488-493"},"PeriodicalIF":2.9,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295669","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