Molecular Genetics & Genomic Medicine最新文献

{"title":"A Novel Biallelic Variant in IHH Causing Acrocapitofemoral Dysplasia in a Pakistani Family.","authors":"Tayyaba Saeed, Nousheen Bibi, Ashfaq Ahmad, Saadullah Khan, Muhammad Ansar, Naveed Wasif, Umm-E- Kalsoom","doi":"10.1002/mgg3.70085","DOIUrl":"10.1002/mgg3.70085","url":null,"abstract":"<p><strong>Background: </strong>Acrocapitofemoral dysplasia (ACFD) is a rare autosomal recessive disorder, characterized by postnatal onset of disproportionate short stature with short limbs, brachydactyly, cone-shaped epiphysis, narrow thorax, and relatively large head. To date, only three homozygous missense mutations have been reported in the signaling amino terminal domain (201-308 amino acids) of the IHH gene in three ACFD families from Belgian, Dutch, and Turkish ethnicities.</p><p><strong>Methods: </strong>In the present study, we have investigated two patients in a Pakistani family affected with ACFD. Whole exome sequencing (WES) followed by Sanger sequencing was carried out for mutational screening. The variant was further validated by in silico modeling and molecular dynamics simulation analysis.</p><p><strong>Results: </strong>Data analysis revealed a novel homozygous missense variant [c.518C>A; p.(Ala173Asp)] in exon 2 of the IHH (NM_002181.4) gene. The variant segregated within the family and was not observed in unaffected ethnically matched controls. In silico modeling and dynamic simulation analysis revealed that the variant disturbed the core structure of the domain and destabilized the loop region and the region surrounding the variant.</p><p><strong>Conclusion: </strong>This study reports the first case of ACFD from Pakistan and identifies the fourth novel missense variant in the IHH gene that led to the broadening of the phenotypic and genotypic spectrum of ACFD.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 3","pages":"e70085"},"PeriodicalIF":1.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Scan of Fifth Finger Clinodactyly.","authors":"Myoung Keun Lee, Noah Herrick, Mary L Marazita, John R Shaffer, Seth M Weinberg","doi":"10.1002/mgg3.70090","DOIUrl":"10.1002/mgg3.70090","url":null,"abstract":"<p><strong>Background: </strong>Fifth finger clinodactyly describes the conspicuous curvature of the fifth digit toward the other digits of the hand. Phenotypic expression can range from mild and almost imperceptible to severe, where function is impacted, and clinical intervention may be required. Although classically considered an autosomal dominant trait based on early family studies, no genes have been mapped for the trait. Further, there is epidemiological evidence that mild (typical-range) fifth finger clinodactyly may have a different etiology than more severe forms.</p><p><strong>Methods: </strong>In this retrospective cross-sectional study, we carried out genome-wide association mapping of common genetic variants for clinodactyly in three cohorts separately and combined results via meta-analysis, treating the trait as either a continuous quantitative variable (n_meta = 631) or a binary outcome (n_meta = 1647).</p><p><strong>Results: </strong>The vast majority of participants in these cohorts exhibited mild forms of clinodactyly. Both the individual cohort results and meta-analyses revealed no genome-wide significant loci. We identified several possible suggestive signals (p < 1 × 10^-6), but these showed no evidence of replication.</p><p><strong>Conclusion: </strong>While our results cannot definitively exclude the contribution of common variants to fifth finger clinodactyly due to the small sample size, they do suggest that the mild form of the trait is unlikely to be related to a major gene effect operating in a simple Mendelian manner.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 3","pages":"e70090"},"PeriodicalIF":1.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approaches to Evaluate Whole Exome Sequencing Data That Incorporate Genetic Intolerance Scores for Congenital Anomalies, Including Intronic Regions Adjacent to Exons.","authors":"Kosuke Taniguchi, Fuyuki Hasegawa, Yuka Okazaki, Asuka Hori, Hiroko Ogata-Kawata, Saki Aoto, Ohsuke Migita, Tomoko Kawai, Kazuhiko Nakabayashi, Kohji Okamura, Kana Fukui, Seiji Wada, Katsusuke Ozawa, Yushi Ito, Haruhiko Sago, Kenichiro Hata","doi":"10.1002/mgg3.70092","DOIUrl":"10.1002/mgg3.70092","url":null,"abstract":"<p><strong>Background: </strong>Whole exome sequencing (WES) aids in diagnosing monogenic diseases, yet > 50% of all cases remain undiagnosed. We aimed to improve diagnostic precision by developing an effective WES-based strategy for detecting congenital anomalies.</p><p><strong>Methods: </strong>Initially, 128 probands with congenital anomalies were assessed using trio-WES and copy number variation analysis-variant interpretation was for exons and splice sites. Thereafter, we reanalyzed the sequence data for undiagnosed cases using the following methods. First, we performed trio-WES analysis, adding genetic intolerance scores annotation. Second, we analyzed all exons, splicing sites, and intron variants for cases with phenotypes suggestive of specific causative genes using SpliceAI. Lastly, using SpliceAI, we analyzed all exons, splicing sites, and intron variants in genetically constrained genes filtered with genetic intolerance scores.</p><p><strong>Results: </strong>Initial analysis diagnosed 51 of 128 cases (39.8%). In the reanalysis, first, we identified novel likely pathogenic variants in MED12 and CCDC22 associated with X-linked diseases. Second, a novel TMEM67 intron variant associated with Meckel syndrome was detected. Finally, a de novo hemizygous pathogenic intronic variant in CASK was identified in a case of intrauterine fetal death.</p><p><strong>Conclusions: </strong>WES analysis, including intronic regions and utilizing genetic intolerance scores, has the potential to efficiently improve diagnostic yield.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 3","pages":"e70092"},"PeriodicalIF":1.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Nonsense GLI3 Variants Are Identified in Two Chinese Families With Polydactyly.","authors":"Yongzhen Qi, Kai Liu, Yuda Wei, Xiaxia Liu, Liangqian Jiang, Juan Teng, Baoqiang Chong, Shuqi Zheng, Xiangyu Zhao, Lin Li","doi":"10.1002/mgg3.70088","DOIUrl":"10.1002/mgg3.70088","url":null,"abstract":"<p><strong>Background: </strong>Polydactyly is a prevalent limb deformity with an autosomal dominant inheritance pattern, manifesting in both syndromic and nonsyndromic forms. It exhibits significant etiological and clinical diversity. This study aims to identify the pathogenic cause in two patients with sub-PHS (sub-Pallister-Hall Syndrome) and PAP (postaxial polydactyly), respectively, from two Chinese pedigrees.</p><p><strong>Methods: </strong>Exome sequencing was performed on patients to screen for potential pathogenic variants. Subsequently, these variants were validated by Sanger sequencing. The c.3342dupC and c.4431dupT mutant plasmids were transfected into HEK293T cells, and the effects of GLI3 mutations on transcription and protein levels were analyzed via qRT-PCR and Western blot. Additionally, Swiss Model was utilized to predict the effects of mutations on protein tertiary structure.</p><p><strong>Results: </strong>The mutations of GLI3 (NM_000168.6: c.3342dupC; p. A1115Rfs*14) (NM_000168.6: c.4431dupT; p. Glu1478Ter) were identified in affected individuals. These mutations were present exclusively in the patients and absent in the healthy individuals. No significant difference in transcription levels between the mutations and wild type was observed. Functional analysis revealed that the truncated variants p. A1115Rfs*14 and p. Glu1478Ter exhibited reduced molecular weight and potential functional impairment due to protein retention.</p><p><strong>Conclusion: </strong>The mutations p. A1115Rfs*14 and p. Glu1478Ter in GLI3 may account for sub-PHS and PAP in the two patients, respectively. This finding expands the mutation and phenotype spectrum associated with GLI3, providing valuable insights for the clinical diagnosis of polysyndactyly.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 3","pages":"e70088"},"PeriodicalIF":1.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incomplete Trisomy Rescue Reveals the Mechanism Underlying Discordance Between Noninvasive Prenatal Screening and Prenatal Diagnosis.","authors":"Yanan Wang, Yong Zhou, Yuqiong Chai, Weiwei Zang, Hongchao Wang, Fan Yin, Qianqian Tan, Zhigang Chen","doi":"10.1002/mgg3.70091","DOIUrl":"10.1002/mgg3.70091","url":null,"abstract":"<p><strong>Background: </strong>Uniparental disomy (UPD) is a specific type of chromosomal variation in which both chromosomes of a homologous pair are inherited from the same parent. It is responsible for a wide range of disorders. Monosomy rescue and trisomy rescue are the two main hypotheses of UPD generation.</p><p><strong>Methods: </strong>An older parturient woman with a positive noninvasive prenatal screening (NIPS) test but a negative prenatal diagnosis was referred to the hospital. Trio whole exome sequencing (trio-WES) and ddPCR were further performed.</p><p><strong>Results: </strong>Utilizing Trio-WES analysis, our research identified a maternal segmental UPD on chromosome 16, characterized by isodisomic genomic segments at the ends of the chromosome arms and heterodisomic genomic segments near the centromere. Moreover, several nuanced signs pointing to the paternal chromosome 16 were discovered, suggesting a low level of trisomy 16 mosaicism. A homozygous missense mutation (c.1499C>T; p.Ala500Val) was also detected in the fetal TBC1D24 gene, passed down from the heterozygous carrier mother. Furthermore, ddPCR analysis verified a 3% mosaic level of trisomy 16.</p><p><strong>Conclusion: </strong>We have quantitatively verified for the first time a combination of trisomy 16 mosaicism and maternal segmental UPD 16 due to incomplete trisomy rescue, illuminating the cause of the mismatch between positive NIPS and negative prenatal diagnoses.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 3","pages":"e70091"},"PeriodicalIF":1.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broadening the Phenotype Spectrum of MECP2 Variants in Men.","authors":"Johannes Lötjönen, Venla Kurra, Hannele Laivuori, Nina Bjelogrlić","doi":"10.1002/mgg3.70056","DOIUrl":"10.1002/mgg3.70056","url":null,"abstract":"<p><strong>Background: </strong>MECP2 variants cause X-chromosome-linked rare developmental syndromes. Typically, the mutation is sporadic, occurs in females and is fatal in men. Accurate genetic and clinical diagnostics are considered essential for the management of symptoms and the development of new treatments. These aims may be difficult to reach before more is known about factors resulting in highly variable clinical pictures among patients carrying the same MECP2 variant. We describe the clinical picture of two brothers carrying the same MECP2 variant and compare them with cases published in the literature.</p><p><strong>Methods: </strong>Most of the MECP2 mutations are known to be de novo mutations, which is why the recurrence of the mutation in the couple's other children is unlikely. Unexpectedly, our routine genetic testing revealed a 23-year-old man (P1) and his younger brother (P2) to carry the same hemizygous pathogenic missense variant c.419C>T, p.(Ala140Val) (transcript NM_004992.3) of MECP2, which was found to be inherited from their presumably asymptomatic mother. Thus, further clinical evaluation and comparison with literature cases was considered necessary.</p><p><strong>Results: </strong>The P1 has a severe syndromic intellectual disorder (ID), whereas his brother has a substantially milder ID predominantly limited to problems in verbal skills. Neither P1 nor his younger brother has been diagnosed with Rett syndrome. The P1 (unlike his younger brother) has several lingual, social and motor difficulties; disruptive behavior was the most difficult symptom to treat. P1's response to several medical and non-medical treatment trials has remained inadequate, thus requiring the patient to be hospitalised for a long time. The literature review revealed that apart from our family, there are five other families with more than one male carrying the same MECP2 p.Ala140Val mutation, such as P1 and P2. The phenotypes of all 24 men from us (n = 2) and others (n = 22) carrying the same, presumably non-lethal mutation show great variability.</p><p><strong>Conclusions: </strong>The p.Ala140Val mutation of MECP2 in males is associated with a rare X-chromosomal developmental disorder with highly variable phenotypes. Further studies are needed to better understand all those influencing factors that can explain phenotypic differences within the same genotype to find optimal medicinal therapies.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70056"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Whole Genome Sequencing Uncovers a Triple Diagnosis: X-Linked Chondrodysplasia Punctata, MECP2-Related Disorder, and Mosaic Jacobs Syndrome.","authors":"Megan Samuels, Kathleen Shields, Paul Hillman, Laura Farach","doi":"10.1002/mgg3.70061","DOIUrl":"10.1002/mgg3.70061","url":null,"abstract":"<p><strong>Background: </strong>Rapid Whole Genome Sequencing (rWGS) is increasingly being used in neonatal intensive care units, as there is growing evidence that rare singe gene disorders present in the neonatal period and early identification can change management. While the diagnostic utility is increased with this broad testing, the possibility of unexpected findings also increases significantly. Here, we present a patient found to have three distinct genetic conditions through rWGS testing, with significant psychosocial and health consequences.</p><p><strong>Methods and results: </strong>This case report describes a patient who was identified with a form of chondrodysplasia punctata, as well as incidental findings of MECP2-related disorder and Jacobs' syndrome. To our knowledge, this is one of the first documented cases of triple genetic diagnoses in the literature, underscoring the expanding clinical utility of rWGS.</p><p><strong>Conclusion: </strong>Our patient represents a unique example of the utility of rWGS in the NICU setting. As two of the three conditions were unexpected results, his case is an important reminder of the possibility of unexpected findings for both providers and families. His case demonstrates the importance of pretest counseling and consenting processes, particularly in an acute setting. It also will add to our understanding of MECP2 variant presentations in males in the future.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70061"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Variant in TUBB4B Causes Progressive Cone-Rod Dystrophy and Early Onset Sensorineural Hearing Loss.","authors":"Margherita Scarpato, Francesco Testa, Anna Nesti, Roberta Zeuli, Rosa Boccia, Gennaro Auletta, Sandro Banfi, Francesca Simonelli, Marianthi Karali","doi":"10.1002/mgg3.70068","DOIUrl":"10.1002/mgg3.70068","url":null,"abstract":"<p><strong>Background: </strong>Sensorineural hearing loss (SNHL) is a frequent manifestation of syndromic inherited retinal diseases (IRDs), exemplified by the very rare form of autosomal-dominant Leber congenital amaurosis with early onset deafness (LCAEOD; OMIM #617879). LCAEOD was first described in 2017 in four families segregating heterozygous missense mutations in TUBB4B, a gene encoding a β-tubulin isotype. To date, only eight more families with similar TUBB4B-associated sensorineural disease (SND) have been reported. Most cases harbored missense variants affecting the same amino acid (Arg391) and only three families segregated variants involving different residues (Tyr310, Arg390).</p><p><strong>Methods: </strong>We performed whole-exome sequencing and a full ophthalmological and audiological examination of the affected members in an Italian family segregating syndromic IRD with early onset deafness.</p><p><strong>Results: </strong>We identified a novel, ultra-rare, disease-causing variant in TUBB4B (NM_006088.6:c.1049A>C) that replaces a highly conserved lysine with threonine at amino acid position 350. The functional impact of the Lys350Thr substitution was supported by protein structure modeling studies. The variant segregates in the family members presenting retinal disease with early onset SNHL. Detailed ophthalmological assessment of the affected subjects diagnosed a progressive cone-rod dystrophy.</p><p><strong>Conclusion: </strong>These findings expand the limited number of disease-causing TUBB4B variants, corroborating their association with SND forms, and suggest Lys350 is an important residue for β-tubulin function. Interestingly, our results demonstrate that TUBB4B mutations can cause cone-dominated retinal phenotypes.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70068"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reevaluation of the Impact of the Novel Likely Pathogenic Variant c.1286_1288delAGA in the ATP8A2 Gene: A 7-Year Follow-Up With Clinical, Genetic, and ACMG Insights in an Iranian Family.","authors":"Samira Kalayinia, Hamed Hesami, Reza Shervin Badv, Maryam Rabbani, Zahra Rezaei, Zohreh Hosseinkhani, Sedighe Nikbakht, Ameneh Sharifi, Bahman Akbari, Siamak Mirab Samiee, Nejat Mahdieh","doi":"10.1002/mgg3.70081","DOIUrl":"10.1002/mgg3.70081","url":null,"abstract":"<p><strong>Background: </strong>Cerebellar ataxia, mental retardation, and dysequilibrium (CAMRQ) syndrome is a rare neurodevelopmental disorder characterized by non-progressive cerebellar ataxia, intellectual disability, and cerebellar atrophy. Despite its rarity, CAMRQ syndrome poses significant challenges due to its heterogeneous genetic etiology and complex clinical presentation. This study details the evolving clinical phenotype over 7 years in a male with CAMRQ4 syndrome caused by an in-frame deletion variant in ATP8A2 gene.</p><p><strong>Methods: </strong>A detailed clinical evaluation was performed, accompanied by tests and imaging studies. Clinical and genetic investigations, including segregation analysis, were carried out to confirm the pathogenicity of the identified variant. The evolving clinical phenotype of the patient, including developmental delay, cerebellar ataxia, and hand-foot crawling, was thoroughly investigated.</p><p><strong>Results: </strong>A 10-year-old male patient with CAMRQ syndrome exhibited typical clinical manifestations including impaired motor coordination, cognitive impairment, and balance disturbances. Genetic analysis revealed a homozygous in-frame deletion variant (c.1286_1288delAGA) in the ATP8A2 gene, implicating ATP8A2 in the pathogenesis of CAMRQ syndrome. This variant was predicted to be likely pathogenic and deleterious, in accordance with its segregation in affected family members. Our findings expand the mutational spectrum of ATP8A2-associated CAMRQ syndrome and underscore the importance of comprehensive genetic testing in diagnosing rare neurological disorders.</p><p><strong>Conclusion: </strong>The identification of an in-frame deletion variant in the ATP8A2 gene enhances our understanding of CAMRQ syndrome and highlights the phenotypic variability of the disorder. Our study contributes to the elucidation of CAMRQ syndrome by identifying a novel genetic variant and elucidating its clinical and genetic implications. Further research is warranted to advance our understanding of CAMRQ syndrome and to improve patient care and management strategies.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70081"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The First Evidence for the Role of ACVR2A Gene Fetal Genotype in Preeclampsia Susceptibility.","authors":"Asal Honarpour, Ahmad Majd, Hossein Sadeghi, Sayedhamid Jamaldini, Maryam Rahimi, Paniz Kazemzadeh, Reza Mirfakhraie","doi":"10.1002/mgg3.70069","DOIUrl":"10.1002/mgg3.70069","url":null,"abstract":"<p><strong>Background: </strong>The activin A receptor type 2A gene (ACVR2A) plays an important role in normal gestation, particularly in decidualization, trophoblastic invasion, and placentation. Although several studies have investigated the association between ACVR2A maternal variants and preeclampsia (PE) susceptibility; however, controversial results were obtained. Moreover, in none of the previous studies, the role of ACVR2A fetal variants was explored. The aim of the present study was to investigate the role of ACVR2A rs1424954 and rs1424941 polymorphisms in PE susceptibility considering the impact of both fetal and maternal genotypes.</p><p><strong>Methods: </strong>For genotyping of ACVR2A rs1424954 and rs1424941, we performed TP-ARMS-PCR on 600 samples, including 400 peripheral blood samples from preeclamptic and normal women and 200 umbilical cord blood samples from each group of pregnant women.</p><p><strong>Results: </strong>Regarding rs1424954, only the fetal genotypes were associated with an increased risk of PE in both dominant and recessive inheritance models (OR = 2.88, 95% CI: 1.58-5.25, p = 0.0005; and OR = 2.43, 95% CI: 1.21-4.87, p = 0.012; respectively). For ACVR2A rs1424941variant, both maternal and fetal heterozygote genotypes were associated with PE susceptibility (OR = 1.57, 95% CI: 1.02-2.04, p = 0.04; and OR = 1.90, 95% CI: 1.02-3.54, p = 0.04; respectively).</p><p><strong>Conclusion: </strong>The present study confirmed the role of fetal ACVR2A polymorphisms in PE pathogenesis for the first time. However, replicated studies in diverse ethnicities are necessary to confirm the role of fetal genotype on susceptibility to PE.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 2","pages":"e70069"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}