Molecular Syndromology最新文献

{"title":"Clinical and Genetic Characteristics of Patients with Unexplained Intellectual Disability/Developmental Delay without Epilepsy.","authors":"Hamide Betul Gerik-Celebi, Hilal Aydin, Hilmi Bolat, Gul Unsel-Bolat","doi":"10.1159/000529018","DOIUrl":"10.1159/000529018","url":null,"abstract":"<p><strong>Introduction: </strong>Global developmental delay (DD), intellectual disability (ID), and autism spectrum disorder (ASD) are mainly evaluated under the neurodevelopmental disorder framework. In this study, we aimed to determine the genetic diagnosis yield using step-by-step genetic analysis in 38 patients with unexplained ID/DD and/or ASD.</p><p><strong>Methods: </strong>In 38 cases (27 male, 11 female) with unexplained ID/DD and/or ASD, chromosomal microarray (CMA) analysis, clinical exome sequencing (CES), and whole-exome sequencing (WES) analysis were applied, respectively.</p><p><strong>Results: </strong>We found a diagnostic rate of only CMA analysis as 21% (8/38) presenting 8 pathogenic and likely pathogenic CNVs. The rate of patients diagnosed with CES/WES methods was 32.2% (10/31). When all pathogenic and likely pathogenic variants were evaluated, the diagnosis rate was 44.7% (17/38). A dual diagnosis was obtained in a case with 16p11.2 microduplication and de novo SNV. We identified eight novel variants: <i>TUBA1A</i> (c.787C>G), <i>TMEM63A</i> (c.334-2A>G), <i>YY1AP1</i> (c.2051_2052del), <i>ABCA13</i> (c.12064C>T), <i>ABCA13</i> (c.13187G>A), <i>USP9X</i> (c.1189T>C), <i>ANKRD17</i> (c.328_330dup), and <i>GRIA4</i> (c.17G>A).</p><p><strong>Conclusion: </strong>We present diagnostic rates of a complementary approach to genetic analysis (CMA, CES, and WES). The combined use of genetic analysis methods in unexplained ID/DD and/or ASD cases has contributed significantly to diagnosis rates. Also, we present detailed clinical characteristics to improve genotype-phenotype correlation in the literature for rare and novel variants.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 3","pages":"208-218"},"PeriodicalIF":1.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9646588","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":"Mutated Transcripts of <i>ZEB2</i> Do Not Undergo Nonsense-Mediated Decay in Mowat-Wilson Syndrome.","authors":"Naz Güleray Lafcı, Beren Karaosmanoglu, Ekim Z Taskiran, Pelin Ozlem Simsek-Kiper, Gülen Eda Utine","doi":"10.1159/000528769","DOIUrl":"10.1159/000528769","url":null,"abstract":"<p><strong>Introduction: </strong>Mowat-Wilson syndrome (MWS) is an autosomal-dominant complex developmental disorder characterized by distinctive facial appearance, intellectual disability, epilepsy, and various clinically heterogeneous abnormalities reminiscent of neurocristopathies. MWS is caused by haploinsufficiency of <i>ZEB2</i> due to heterozygous point mutations and copy number variations.</p><p><strong>Case presentation: </strong>We report on two unrelated affected individuals with novel <i>ZEB2</i>indel mutations, molecularly confirming the diagnosis of MWS. Quantitative real-time polymerase chain reaction (PCR) for the comparison of total transcript levels and allele-specific quantitative real-time PCR were also performed and demonstrated that the truncating mutations did not lead to nonsense-mediated decay as expected.</p><p><strong>Conclusion: </strong><i>ZEB2</i> encodes a multifunctional pleiotropic protein. Novel mutations in <i>ZEB2</i> should be reported in order that genotype-phenotype correlations might be established in this clinically heterogeneous syndrome. Further cDNA and protein studies may help elucidate the underlying pathogenetic mechanisms of MWS since nonsense-mediated RNA decay was found to be absent in only a few studies including this study.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 3","pages":"258-265"},"PeriodicalIF":1.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9652839","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":"Identification of a Novel <i>IQCE</i> Large Deletion through Copy Number Variant Analysis from Whole-Exome Sequencing Data of a Patient with Postaxial Polydactyly Type A7.","authors":"Faidon-Nikolaos Tilemis, Nikolaos M Marinakis, Konstantina Kosma, Florentia Fostira, Joanne Traeger-Synodinos","doi":"10.1159/000527777","DOIUrl":"10.1159/000527777","url":null,"abstract":"<p><strong>Introduction: </strong>Non-syndromic polydactyly has been associated with pathogenic variants in 11 genes until today, including <i>IQCE</i> gene. More precisely, loss-of-function of <i>IQCE</i> is associated with the autosomal recessive disorder postaxial polydactyly type A7 (PAPA7, MIM #617642).</p><p><strong>Case presentation: </strong>A 3-year-old female patient was referred to our genetics department with postaxial polydactyly, syndactyly, brachydactyly, and hypoplastic teeth. Through whole-exome sequencing (WES), a pathogenic <i>IQCE</i> variant was identified (c.895_904del) in the homozygous state, which adequately explained the disease phenotype of our patient. However, copy number variant (CNV) analysis from WES data, using ExomeDepth, revealed a novel, likely pathogenic large deletion involving <i>IQCE</i> genomic regions (DEL:chr7:2606751_2641098) encompassing exons 2-18 of the gene.</p><p><strong>Conclusion: </strong><i>IQCE</i> gene codes for a 695-amino acid protein located at the base of the primary cilia that positively regulates the Hedgehog signaling pathway. This case report represents the first description of a large deletion in <i>IQCE</i> and indicates that implementation of ExomeDepth in routine WES analysis can contribute valuable information toward elucidating the correct etiology of rare genetic diseases, increasing the diagnostic yield, and minimizing the need for additional tests.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 3","pages":"225-230"},"PeriodicalIF":1.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9655797","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":"Dicentric Recombinant Chromosome 18 due to Maternal Paracentric Inversion Analyzed by Array CGH.","authors":"Özlem Anlaş, Akgün Ölmez, Birsen Karaman, Füsun Düzcan, Selçuk Yüksel, Funda Tümkaya, Gülseren Bağcı, Cavidan Nur Semerci Gündüz","doi":"10.1159/000527160","DOIUrl":"10.1159/000527160","url":null,"abstract":"<p><strong>Introduction: </strong>Chromosomal abnormalities are mostly found in 0.5-0.8% of live-born infants with developmental and morphological defects. Paracentric inversions are structural intrachromosomal rearrangements resulting in a risk of chromosomally unbalanced gametes in carriers.</p><p><strong>Case presentation: </strong>Herein, we report a patient with dicentric rearrangement of chromosome 18 due to maternal paracentric inversion of chromosome 18. The patient was a girl, aged 3 years and 11 months. She was referred due to multiple congenital abnormalities, severe intellectual disability, and motor retardation. She had microcephaly, prominent metopic suture, synophrys, epicanthic folds, telecanthus, wide-set alae nasi, wide columella, bilateral cleft lip and palate, pectus carinatum, umbilical hernia, pes planus, and anteriorly displaced anus. She had bilateral external auditory canal stenosis and mild right-sided and moderate left-sided sensorineural hearing loss. Echocardiography showed secundum-type atrial septal defect and mild tricuspid failure. Brain magnetic resonance imaging showed only thinning of posterior areas of the corpus callosum. Chromosome analysis showed 46,XX,dic rec(18) by GTG and C banding. Dicentric chromosome was confirmed by fluorescence in situ hybridization analysis. Paternal karyotype was normal 46,XY but maternal chromosome analysis showed a paracentric inversion in chromosome 18 with 46,XX,inv(18)(q11.2?q21.3?) karyotype. Array CGH was performed on a peripheral blood sample from the patient and showed duplication at 18p11.32p11.21 and 18q11.1q11.2, and deletion at 18q21.33q23. The patient's final karyotype is arr 18p11.32p11.21(64,847_15,102,598)×3,18q11.1q11.2(18,542,074_22,666,470)×3,18q21.33q23(59,784,364_78,010,032)×1.</p><p><strong>Discussion: </strong>To the best of our knowledge, this is the first report of a patient with dicentric chromosome 18 due to a parental paracentric inversion of chromosome 18. We present the genotype-phenotype correlation with literature review.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 3","pages":"246-253"},"PeriodicalIF":1.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9658974","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":"Identification of a Novel Nonsense Variant in the <i>DLL3</i> Gene Underlying Spondylocostal Dysostosis in a Consanguineous Pakistani Family.","authors":"Feroz Khan, Abida Arshad, Asmat Ullah, Ellen Steenackers, Geert Mortier, Wasim Ahmad, Muhammad Arshad, Sarmir Khan, Amir Hayat, Ikram Khan, Muhammad Asim Khan, Wim Van Hul","doi":"10.1159/000527043","DOIUrl":"10.1159/000527043","url":null,"abstract":"<p><strong>Introduction: </strong>Spondylocostal dysostosis (SCD) is characterized by multiple vertebral abnormalities associated with abnormalities of the ribs. Five genes causative for the disease have been identified. These include <i>DLL3</i> (OMIM *602768), <i>MESP2</i> (OMIM #608681), <i>LFNG</i> (OMIM #609813), <i>TBX6</i> (OMIM *602427), and <i>HES7</i> (OMIM *608059).</p><p><strong>Methods: </strong>In the current study, we investigated a Pakistani consanguineous family segregating spondylocostal dysotosis. Whole-exome sequencing (WES) followed by Sanger sequencing was performed using DNA of affected and unaffected individuals to identify pathogenic variant(s). The identified variant was interpreted using ACMG classification. Literature review was performed to summarize currently known mutated alleles of <i>DLL3</i> and the underlying clinical phenotypes.</p><p><strong>Results: </strong>Clinical examination using anthropometric measurements and radiographs diagnosed the patients to be afflicted with SCD. Pedigree analysis of the affected family showed an autosomal recessive inheritance pattern of the disease. WES followed by Sanger sequencing identified a novel homozygous nonsense variant (<i>DLL3</i>(NM_016941.4): c.535G>T; p.Glu179Ter) in the <i>DLL3</i> gene located on chromosome 19q13.2.</p><p><strong>Conclusion: </strong>The study will be helpful in carrier testing and genetic counseling to prevent segregation of the disease to the next generations within this family. It also provides knowledge for clinicians and researchers in search of a better understanding of SCD anomalies.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 3","pages":"191-200"},"PeriodicalIF":1.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9658977","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":"Report on a Case with Moreno-Nishimura-Schmidt Overgrowth Syndrome: A Clinically Delineated Disease Yet of an Unknown Origin!","authors":"Cybel Mehawej, Eliane Chouery, Ghada Al Hage Chehade, Yosra Bejaoui, Daniel Mahfoud, Maya Gerges, Valérie Delague, Nady El Hajj, Andre Megarbane","doi":"10.1159/000527215","DOIUrl":"10.1159/000527215","url":null,"abstract":"<p><strong>Introduction: </strong>Overgrowth syndromes are a heterogeneous group of genetic disorders characterized by excessive growth, often accompanied by additional clinical features, such as facial dysmorphism, hormonal imbalances, cognitive impairment, and increased risk for neoplasia. Moreno-Nishimura-Schmidt (M-N-S) overgrowth syndrome is a very rare overgrowth syndrome characterized by severe pre- and postnatal overgrowth, dysmorphic facial features, kyphoscoliosis, large hands and feet, inguinal hernia, and distinctive skeletal features. The clinical and radiological features of the disorder have been well delineated, yet its molecular pathogenesis remains unclear.</p><p><strong>Case presentation: </strong>We report on a Lebanese boy with M-N-S syndrome, whose clinical manifestations were compared with those of previously reported 5 affected individuals. Whole-exome sequencing combined with comparative genome hybridization analysis failed to delineate the molecular basis of the phenotype. However, epigenetic studies revealed a different methylation status of several CpG sites between him and healthy controls, with methyltransferase activity showing the most significant enrichment.</p><p><strong>Conclusion: </strong>An additional case of M-N-S syndrome recapitulated the clinical and radiological manifestations described in the previous reports. The data in the epigenetic studies implicated that abnormal methylations might play an essential role in development of the disease phenotype. However, additional studies in a clinically homogeneous cohort of patients are crucial to confirm this hypothesis.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 3","pages":"219-224"},"PeriodicalIF":1.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9708995","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 New Youngest Case of Grange Syndrome with a Novel Biallelic Pathogenic Variant in <i>YY1AP1</i>.","authors":"Taner Karakaya, Ayberk Turkyilmaz, Deniz Eris, Mehtap Kaya, Kupra Oksuz, Meltem Aygul Eryigit, Gizem Gönen","doi":"10.1159/000527785","DOIUrl":"10.1159/000527785","url":null,"abstract":"<p><strong>Introduction: </strong>Grange syndrome (OMIM 602531) is characterized by a constellation of symptoms of hypertension, stenosis, or occlusion of different arteries (including the cerebral, renal, abdominal, and coronary vessels) with a variable occurrence of brachysyndactyly, bone fragility, and congenital heart defects. Learning disabilities were also reported in some cases. Biallelic pathogenic variants in <i>YY1AP1</i> are associated with the syndrome. Only 14 individuals with this ultra-rare syndrome (12 of them were molecularly confirmed) have hitherto been reported in the literature.</p><p><strong>Case presentation: </strong>We herein describe a 1^1/2-year-old additional female case of Grange syndrome with hypertension, patent ductus arteriosus, and brachysyndactyly who was subsequently confirmed to carry a novel homozygous frameshift variant (c.2291del; p.Pro764Leufs*12) in the <i>YY1AP1</i> gene through whole-exome sequencing.</p><p><strong>Conclusion: </strong>This report extends the allelic spectrum in Grange syndrome and helps provide insight into the potential role of YY1AP1 in the regulation of cellular processes.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 3","pages":"239-245"},"PeriodicalIF":1.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9658978","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":"Triosephosphate Isomerase Deficiency: E105D Mutation in Unrelated Patients and Review of the Literature.","authors":"Arzu Selamioğlu, Meryem Karaca, Mehmet Cihan Balcı, Hüseyin Kutay Körbeyli, Aslı Durmuş, Edibe Pembegül Yıldız, Serap Karaman, Gülden Fatma Gökçay","doi":"10.1159/000528192","DOIUrl":"10.1159/000528192","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic haemolytic anaemia, increased susceptibility to infections, cardiomyopathy, neurodegeneration, and death in early childhood are the clinical findings of triosephosphate isomerase (TPI) deficiency, which is an ultra-rare disorder. The clinical and laboratory findings and the outcomes of 2 patients with TPI deficiency are reported, with a review of cases reported in the literature.</p><p><strong>Case presentation: </strong>Two unrelated patients with haemolytic anaemia and neurologic findings who were diagnosed as having TPI deficiency are presented. Neonatal onset of initial symptoms was observed in both patients, and the age at diagnosis was around 2 years. The patients had increased susceptibility to infections and respiratory failure, but cardiac symptoms were not remarkable. Screening for inborn errors of metabolism revealed a previously unreported metabolic alteration determined using tandem mass spectrometry in acylcarnitine analysis, causing elevated propionyl carnitine levels in both patients. The patients had p.E105D (c.315G>C) homozygous mutations in the <i>TPI1</i> gene. Although severely disabled, both patients are alive at the ages of 7 and 9 years.</p><p><strong>Discussion: </strong>For better management, it is important to investigate the genetic aetiology in patients with haemolytic anaemia with or without neurologic symptoms who do not have a definitive diagnosis. The differential diagnosis of elevated propionyl carnitine levels using tandem mass spectrometry screening should also include TPI deficiency.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 3","pages":"231-238"},"PeriodicalIF":1.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9658980","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":"Differential Diagnosis of Pulmonary Veno-Occlusive Disease and/or Pulmonary Capillary Hemangiomatosis after Identification of Two Novel <i>EIF2AK4</i> Variants by Whole-Exome Sequencing.","authors":"Jong Eun Park, Sung-A Chang, Shin Yi Jang, Kyung Soo Lee, Duk-Kyung Kim, Chang-Seok Ki","doi":"10.1159/000527524","DOIUrl":"10.1159/000527524","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension. Pulmonary arterial hypertension (PAH) and PVOD/PCH are clinically similar, but there is a risk of drug-induced pulmonary edema when PCH patients receive the PAH therapy. Therefore, early diagnosis of PVOD/PCH is important.</p><p><strong>Objectives: </strong>We report the first case in Korea of PVOD/PCH in a patient carrying compound heterozygous pathogenic variants in the <i>EIF2AK4</i> gene.</p><p><strong>Case description and method: </strong>A 19-year-old man who was previously diagnosed with idiopathic PAH suffered from dyspnea on exertion for 2 months. He had a reduced lung diffusion capacity for carbon monoxide (25% predicted). Chest computed tomography images showed diffusely scattered ground-glass opacity nodules in both lungs with an enlarged main pulmonary artery. For the molecular diagnosis of PVOD/PCH, whole-exome sequencing was performed for the proband.</p><p><strong>Results: </strong>Exome sequencing identified two novel <i>EIF2AK4</i> variants, c.2137_2138dup (p.Ser714Leufs*78) and c.3358-1G>A. These two variants were classified as pathogenic variants according to the 2015 American College of Medical Genetics and Genomics guidelines.</p><p><strong>Conclusions: </strong>We identified two novel pathogenic variants (c.2137_2138dup and c.3358-1G>A) in the <i>EIF2AK4</i> gene. Identification of possible pathogenic gene variants by whole-exome sequencing or panel sequencing is recommended as a guide to adequate treatment of patients with pulmonary hypertension.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 3","pages":"254-257"},"PeriodicalIF":1.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9652838","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 Genetics Study in the Foreskin of Boys with Hypospadias.","authors":"Irem Inanc, Dincer Avlan, Damla Eker, Hakan Gurkan","doi":"10.1159/000527405","DOIUrl":"10.1159/000527405","url":null,"abstract":"<p><strong>Introduction: </strong>Hypospadias is a malformation of the genitourinary system in males, characterized by the placement of the urethral opening in the ventral surface of the penis. Although controversies continue about etiology, endocrine disrupting chemicals that disrupt normal endocrine signaling at the receptor or signal transduction level are thought to play an essential role in etiology. This study aimed to investigate the receptor gene expressions of the sex hormones and <i>FGFR2, HOXA13</i>, and <i>TGFB1</i>, which are considered to play an essential role in developing hypospadias.</p><p><strong>Methods: </strong>The samples from the foreskin of 26 patients with hypospadias and 26 healthy children who underwent circumcision operations were collected. <i>ESR1, AR, FGFR2, HOXA13</i>, and <i>TGFB</i> gene expressions were investigated by real-time PCR in samples obtained during surgery.</p><p><strong>Results: </strong>In the hypospadias group, <i>ESR1</i> expression was increased (<i>p</i> = 0.013), and <i>AR</i> and <i>FGFR2</i> expressions were decreased, which were found to be statistically significant (<i>p</i> = 0.027 and <i>p</i> = 0.003, respectively). There was no statistically significant difference between hypospadias and control groups in <i>TGFB</i>and <i>HOXA13</i>expression levels (<i>p</i> > 0.05).</p><p><strong>Discussion: </strong>The results suggest that sex hormone receptors and FGFR2 may play an essential role in developing male external genital structures at the gene level. The defects in the expression of these genes can contribute to understanding the development of hypospadias.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 3","pages":"185-190"},"PeriodicalIF":1.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9658975","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}