Molecular Syndromology最新文献

{"title":"<i>CHAMP1</i>-Related Neurodevelopmental Disorder: Two Turkish Cases with Novel Truncating Variants and Literature Review.","authors":"Zehra Manav Yigit, Pelin Ozyavuz Cubuk, Kamil Utku Bayrak, Mehmet Bugrahan Duz, Adnan Yuksel","doi":"10.1159/000551451","DOIUrl":"10.1159/000551451","url":null,"abstract":"<p><strong>Introduction: </strong><i>CHAMP1</i>-related neurodevelopmental disorder (<i>CHAMP1</i>-NDD; neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features; MIM: 616579) is a rare autosomal-dominant condition caused by de novo truncating variants leading to haploinsufficiency. The phenotype is characterized by global developmental delay, intellectual disability, severe speech impairment, hypotonia, distinctive craniofacial features, and variable multisystem involvement.</p><p><strong>Case presentation: </strong>We describe two unrelated girls harboring novel de novo truncating <i>CHAMP1</i> variants. Both presented with global developmental delay, profound speech impairment, hypotonia, postnatal growth impairment, and characteristic craniofacial features. Neuroimaging demonstrated normal findings in 1 patient and a thin corpus callosum in the other. Additional manifestations included high-grade vesicoureteral reflux in one individual and sensory dysregulation, reduced pain sensitivity, early-onset hyperphagia, and recurrent respiratory infections in the other. Perinatal complications were noted in one case; however, the overall phenotype was considered primarily attributable to the underlying genetic diagnosis. Exome sequencing identified heterozygous truncating variants, NM_032436.4:c.2081_2082del; p.Ser694* and NM_032436.4:c.2062dup; p.Glu688Glyfs*8, both confirmed as de novo and classified as likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) criteria.</p><p><strong>Conclusion: </strong>These cases expand the mutational spectrum of <i>CHAMP1</i> and further delineate the phenotypic variability of this disorder, highlighting under-recognized systemic and behavioral features. Recognition of these additional clinical observations may facilitate earlier diagnosis and multidisciplinary management, although further studies in larger cohorts are required to clarify their clinical relevance.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147934809","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":"Syndromic Alobar Holoprosencephaly Associated with a de novo 2p21p16.2 Contiguous Gene Deletion: A Neonatal Case Report.","authors":"Ramazan Keçeci, Hayriye Nermin Keçeci, Melek Büyükeren, Fatma Hilal Yılmaz, Beyza Özcan","doi":"10.1159/000551509","DOIUrl":"10.1159/000551509","url":null,"abstract":"<p><strong>Background: </strong>Chromosome 2p21 harbors <i>SIX3</i>, a major driver gene for holoprosencephaly (HPE). Large copy number variants (CNVs) overlapping 2p21p16.2 are rare and may present with pleiotropic congenital anomalies.</p><p><strong>Case presentation: </strong>A female neonate born at 27 weeks (1,000 g) after placental abruption was diagnosed with distinguishable craniofacial features, alobar HPE, agenesis of the corpus collosum (ACC), and a 6-mm atrial septal defect. Chromosomal microarray analysis revealed a heterozygous 11.3 Mb interstitial deletion at arr[GRCh38] 2p21p16.2(43075433_54379379)x1, containing entire <i>SIX3</i>, <i>EPCAM</i>, and a cluster of mismatch repair (MMR) genes such as <i>MSH2 and MSH6</i>. The parents do not have dysmorphic features, their karyotype analysis was normal, and based on the available data, the CNV was considered de novo.</p><p><strong>Conclusion: </strong>The patient's phenotype is consistent with <i>SIX3</i> haploinsufficiency leading to severe forebrain division insufficiency; the adjacent MMR deletion defines the Lynch susceptibility locus. We emphasize the need to consider the risk of cancer in later life, in addition to the currently available findings.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147934806","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":"An Atypical Neurosensory-Predominant Presentation Associated with a Homozygous <i>NDUFS3</i> Variant: A Diagnostic Challenge Involving Retinal and Hearing Phenotypes.","authors":"Hacer Basan, Emin Emre Kurt, Çiğdem Seher Kasapkara","doi":"10.1159/000551507","DOIUrl":"10.1159/000551507","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondrial complex I deficiency represents a major cause of pediatric mitochondrial disease and is associated with a broad phenotypic spectrum, classically including Leigh syndrome and severe neurodegenerative presentations. Variants in <i>NDUFS3</i>, encoding a core structural subunit of complex I, are rare and most often linked to severe multisystem involvement. However, emerging reports suggest that <i>NDUFS3</i> variants may be associated with more heterogeneous and atypical clinical manifestations. Here, we describe a child with a neurosensory-predominant phenotype presenting a diagnostic challenge involving retinal and auditory findings in the context of a homozygous <i>NDUFS3</i> variant.</p><p><strong>Case presentation: </strong>A girl born to consanguineous parents presented with global developmental delay, bilateral digital contractures, impaired visual responses, and progressive hearing difficulties. Ophthalmologic evaluation revealed Stargardt-like maculopathy, while audiologic assessment confirmed bilateral sensorineural hearing loss. Neurological examination showed mild motor delay without neuroregression. Brain magnetic resonance imaging and spectroscopy were unremarkable, and no cardiomyopathy or metabolic crises were observed. Whole-exome sequencing identified a homozygous NDUFS3 c.721G>A (p.Ala241Thr; rs776795187) variant, classified as a variant of uncertain significance and predicted to be deleterious by multiple in silico tools (SIFT, PolyPhen-2, MutationTaster, and CADD). Heterozygous variants were also detected in ABCA4 and HMCN1. Parental segregation analysis was not available at the time of evaluation. Supportive mitochondrial therapy was initiated, and the patient remained clinically stable during long-term follow-up, with nonprogressive neurosensory findings.</p><p><strong>Conclusion: </strong>This case highlights the diagnostic complexity of interpreting atypical neurosensory-predominant phenotypes in mitochondrial disease. While the homozygous NDUFS3 variant may contribute to systemic mitochondrial vulnerability, the coexistence of heterozygous retinal gene variants suggests a possible modifying or oligogenic effect. Rather than defining a distinct monogenic entity, this report underscores the importance of cautious genotype-phenotype correlation and comprehensive genetic evaluation in children presenting with combined retinal and auditory involvement.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151367","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 Systematic Bioinformatic Analysis of the miRNA Pathway in Inborn Errors of Amino Acid Metabolism Disorders.","authors":"Harun Bayrak, Parisa Sharafi, Mustafa Kılıç","doi":"10.1159/000551508","DOIUrl":"10.1159/000551508","url":null,"abstract":"<p><strong>Introduction: </strong>Inborn errors of amino acid metabolism (IEAAM) are genetic defects that lead to the toxic accumulation of metabolites. While the genetic basis of these intoxication-type disorders is well-established, the regulatory role of microRNAs in their pathogenesis remains poorly synthesized. This systematic bioinformatic analysis aims to identify and validate specific miRNA-gene interactions that modulate key metabolic pathways in IEAAM.</p><p><strong>Methods: </strong>A systematic literature search was conducted across PubMed and Scopus databases. We integrated identified miRNAs with metabolic genes using prediction tools (e.g., miRWalk, miRDB) and validated these interactions through functional pathway analysis using KEGG, DisGeNET, and PubChem database integration.</p><p><strong>Results: </strong>Our analysis identified a consistent network of miRNAs associated with amino acid metabolism. Specifically, six miRNAs (mmu-miR-409-5p, hsa-miR-3944-3p, rno-miR-125b-5p, hsa-miR-145-5p, hsa-miR-5195-3p, and hsa-miR-1202) were bioinformatically validated to target key genes such as <i>FAH</i>, <i>DBT</i>, <i>CBS</i>, <i>PSAT1</i>, and <i>ARG1</i>. These miRNAs are significantly enriched in metabolic pathways (KEGG) and associated with clinical phenotypes including epilepsy and intoxication-related metabolic crises.</p><p><strong>Conclusion: </strong>This computational study provides the first systematic evidence of a conserved miRNA-gene regulatory network in aminoacidopathies. By identifying these six key regulatory miRNAs, our findings offer novel insights into the epigenetic modulation of metabolic blocks and highlight potential targets for future miRNA-based therapeutic interventions in IEAAM.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786094","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":"IFT43-Related Cranioectodermal Dysplasia Type 3: Clinical and Molecular Insights from the First Reported Turkish Patient.","authors":"Sinem Kocagil, Hilal Gölcür, Sabri Aynacı, Oğuz Çilingir","doi":"10.1159/000551376","DOIUrl":"10.1159/000551376","url":null,"abstract":"<p><strong>Introduction: </strong>Cranioectodermal dysplasias (CEDs) are clinically and genetically heterogenous group of rare autosomal recessive ciliopathies characterized by craniofacial dysmorphism, skeletal and ectodermal anomalies, growth retardation, and renal involvement. To date, approximately 100 affected individuals have been reported in the literature and IFT43-associated CED type 3 is one of the rarest subtypes.</p><p><strong>Case presentation: </strong>We report the third patient diagnosed with CED type 3, presenting with typical features of the disorder, including postaxial polydactyly, dolichocephaly, frontal bossing, and ectodermal abnormalities, along with normal neurological development, and follow-up findings over a 7-year period. Whole-exome sequencing revealed compound heterozygous pathogenic variants in the <i>IFT43</i> gene NM_001102564.3:c.55-1G>A and NM_001102564.3:c.175C>T (p.Arg59*).</p><p><strong>Conclusion: </strong>We believe this patient contributes to the limited number of reported <i>IFT43</i>-related CED type 3 cases and expands our knowledge of this rare ciliopathy. Further research is required to more precisely characterize the clinical presentation and to better understand genotype-phenotype associations.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147943269","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":"Investigation of the Expression Levels of Exosomal miRNAs in the Patients: Myocardial Infarction with Nonobstructive Coronary Arteries.","authors":"Sinem Yalcintepe, Servet Altay, Melik Demir, Hazal Sezginer Guler, Drenushe Zhuri, Necdet Sut, Selma Demir, Engin Atli, Emine Ikbal Atli, Damla Eker, Hakan Gurkan","doi":"10.1159/000551363","DOIUrl":"10.1159/000551363","url":null,"abstract":"<p><strong>Introduction: </strong>Myocardial infarction with nonobstructive coronary artery disease (MINOCA) poses a challenge for diagnosis and treatment because of its heterogeneous etiology. The mechanisms underlying MINOCA are diverse and include plaque disruption, coronary spasm, microvascular dysfunction, and thromboembolism. However, the specific molecular pathways involved are not fully understood. MicroRNAs (miRNAs) are known as potential biomarkers and regulators of various cardiovascular diseases. In our study, we aimed to investigate the relationship between MINOCA and exosomal miRNA expression and to determine the potential of these exosomal miRNAs as biomarkers for prognosis, diagnosis, and treatment.</p><p><strong>Methods: </strong>Three groups were included in the study: (1) the MINOCA group, (2) the myocardial infarction with obstructive coronary artery disease group, and (3) the healthy control group. Exosomal miRNA isolation was performed from all participants, and the expression levels of hsa-miR-16-5p, hsa-miR-92a-3p, hsa-miR-487a-5p, and hsa-miR-490-3p were analyzed by quantitative real-time PCR (polymerase chain reaction). ΔΔCt values were determined, and statistical analyses were performed after these values were obtained.</p><p><strong>Results: </strong>Statistical analysis of hsa-miR-16-5p, hsa-miR-92a-3p, hsa-miR-487a-5p, and hsa-miR-490-3p revealed that the expression levels of hsa-miR-490-3p were significantly different between the groups in the MINOCA group (<i>p</i> = 0.022). hsa-miR-16-5p was found to be closely related to the statistical significance level (<i>p</i> = 0.078). hsa-miR-92a-3p and hsa-miR-487a-5p were not significantly different between the groups.</p><p><strong>Conclusion: </strong>Our study revealed that miR-490-3p, which was detected at a statistically significant level in the MINOCA group, is an effective biomarker in MINOCA patients. This miRNA has been reported in only a few studies on myocardial infarction, and our study is the first to report it in relation to MINOCA. The fact that hsa-miR-16-5p is close to statistical significance, whereas statistical significance was not detected for hsa-miR-92a-3p and hsa-miR-487a-5p, indicates that studies with a larger number of individuals are needed.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147870077","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":"Gillespie Syndrome: Greek Patient with Novel Mutation and Atypical Presentation - Expansion of the Phenotype and Literature Review.","authors":"Maria Lithoxopoulou, Maria Alvanou, Efterpi Pavlidou, Tatiana Tziola, Evgenia Babatseva, Eftychia Drogouti, Despoina Tramma, Magdalini Sterpi, Ariadni Papadopoulou, Aikaterini K Seliniotaki, Elissavet Diamanti, Christos Tsakalidis, Asimina Mataftsi, Athina Ververi","doi":"10.1159/000551342","DOIUrl":"10.1159/000551342","url":null,"abstract":"<p><strong>Introduction: </strong>Gillespie syndrome is characterized by bilateral aniridia, cerebellar hypoplasia leading to ataxia, congenital hypotonia, and variable degrees of intellectual disability. The condition is attributed to pathogenic variants in <i>ITPR1</i>, either in a biallelic manner or as heterozygous dominant-negative mutations.</p><p><strong>Case presentation: </strong>Herein, we report the case of a male neonate with generalized hypotonia, and bilateral aniridia, identified during routine newborn eye screening. His abdominal ultrasound revealed a left dysplastic pleiocystic kidney, and his brain magnetic resonance imaging showed mega cisterna magna. In the second month of life, he presented with intestinal malrotation requiring surgical repair. Whole exome sequencing revealed a homozygous deletion of exons 3 and 4 in the <i>ITPR1</i> gene, confirmed by molecular karyotype (array CGH). The patient was diagnosed with Gillespie syndrome, consistent with his ophthalmological and neurological findings.</p><p><strong>Conclusion: </strong>Urinary and gastrointestinal issues such as a pleiocystic kidney and malrotation have not previously been associated with Gillespie syndrome. While these findings may be coincidental, they could represent new phenotypic features of the condition.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147870097","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":"Genetic Skeletal Disorders with Defects in Glycosaminoglycan Biosynthesis.","authors":"Yuko Tsujioka, Pelin Ozlem Simsek Kiper, Sheila Unger, Atsuhiko Handa, Tatsuo Kono, Masahiro Jinzaki, Antonio Rossi, Andrea Superti-Furga, Gen Nishimura","doi":"10.1159/000551137","DOIUrl":"10.1159/000551137","url":null,"abstract":"<p><strong>Background: </strong>Proteoglycans are a major component of the connective tissue matrix, which consists of a core protein and covalently attached glycosaminoglycan (GAG) chains, which are highly sulfated polysaccharides with a tetrasaccharide linker for the core protein attachment. Impaired synthesis or degradation of GAG causes genetic disorders. In the 1950s, deficient lysosomal GAG degradation was discovered in mucopolysaccharidoses. In the 1990s, a defective enzyme for GAG synthesis was implicated in a variant of Ehlers-Danlos syndrome and an impaired GAG sulfation in diastrophic dysplasia. Newer studies have uncovered that abnormal GAG synthesis causes a large group of genetic skeletal disorders with joint and skin abnormalities.</p><p><strong>Summary: </strong>The prototype of this group includes diastrophic dysplasia and Desbuquois dysplasia. The former is attributed to abnormal GAG sulfation, while the latter to impaired GAG chain elongation. Defective linker formation causes distinctive phenotypes termed linkeropathy. Moreover, there remain many disorders with defective GAG synthesis, in which the phenotypes are poorly documented and thus the clinical suspicion and even interpretation of molecular findings are challenging. Here, we attempt to review the skeletal manifestations of abnormal GAG synthesis disorders, based on our own experiences and previous reports. Each disorder has distinct clinical and radiological features, but they share some common skeletal manifestations, such as distal humeral hypoplasia, misshapen proximal femora, accelerated carpal ossification, and malsegmentation of the short tubular bones.</p><p><strong>Key message: </strong>Awareness of the phenotypic similarities and differences among this group of disorders facilitates our clinical and genetic practices for affected individuals.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844479","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":"<i>STXBP1</i> Encephalopathy: Cannabidiol as a Treatment Option and Expansion of the Genotype-Phenotype Spectrum - Case Reports.","authors":"Adeline Ngoh, Heming Wei, Tong Hong Yeo, Janardhan Krishnappa, Simon Ling, Ene Choo Tan, Derrick Wei Shih Chan","doi":"10.1159/000550657","DOIUrl":"10.1159/000550657","url":null,"abstract":"<p><strong>Introduction: </strong><i>STXBP1</i> encodes syntaxin-binding protein 1, a protein with a role in trafficking of syntaxin-1 to the synapse and synaptic neurotransmitter release. Mutations in <i>STXBP1</i> are associated with a wide range of neurodevelopmental phenotypes, including epilepsy, intellectual disability, and movement disorders.</p><p><strong>Case series: </strong>We report 4 individuals with pathogenic variants in <i>STXBP1</i>, including 2 previously unreported variants, presenting with a range of severity. One severely affected child with refractory seizures and distressing dystonia responded well to treatment with cannabidiol (CBD), with both seizure cessation and improvement in tone.</p><p><strong>Conclusion: </strong><i>STXBP1</i> variants are associated with significant phenotypic pleiotropy and a wide spectrum of severity. CBD may be beneficial for severely affected individuals with seizures and movement disorders that are refractory to conventional treatments.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13021239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575993","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":"Evaluation of Cytogenetic and Molecular Genetic Tests in Patients with Short Stature.","authors":"Gülçin Arslan, Benay Turan, Tayfun Çinleti, Hatice Yelda Yalçın, Özge Özer Kaya, Sevim Onguner, Gülümay Vural, Müge Nasırlı, Hakan Birinci, Emrullah Arslan, Berna Eroğlu Filibeli, Eren Er, Bumin Nuri Dündar","doi":"10.1159/000551005","DOIUrl":"10.1159/000551005","url":null,"abstract":"<p><strong>Introduction: </strong>Short stature is among the most common endocrinological diseases in childhood. The investigation of syndromic or non-syndromic genetic causes provides important data for etiology. This study aimed to present the frequency of genetic variant detection in cases in which genetic studies were performed for short stature in our clinic and the clinical characteristics of patients in whom clinically significant variants were detected.</p><p><strong>Methods: </strong>Two hundred forty-six patients who applied to our center with complaints of short stature and underwent genetic testing during a 1.5-year period were included. Anthropometric measurements, history and physical examination findings, and tests for the etiology of short stature were recorded retrospectively for all patients with pathological results.</p><p><strong>Results: </strong>Genetic tests were performed for a total of 228 children with short stature, of whom 39 (17.2%) were male and 189 (82.8%) were female. Pathogenic variants were identified in 56 (24.5%) of 228 patients. The mean height standard deviation score (SDS) of all patients was -2.63 ± 1.42. The height SDS of the patients with the gene variant was -2.73 ± 1.32. Pathological results were detected in 26 of 113 patients (23%) who underwent karyotype analysis, while clinically significant pathogenic results were obtained in 2 of 67 patients (2.9%) who underwent microarray analysis, 9 of 76 patients (30.8%) who underwent short stature panel analysis, 5 of 18 patients (27.7%) who underwent RASopathy panel testing, 7 of 37 patients (15%) who underwent SHOX MLPA, and 7 of 17 patients (6.9%) who underwent skeletal dysplasia panel analysis.</p><p><strong>Conclusion: </strong>Different genetic causes and pathophysiological processes underlie isolated and/or syndromic short stature. With the development in genetics, it is becoming easier and more important to elucidate the etiology of short stature, as in other diseases. Our study supports the significance of genetic diagnosis in patients with short stature, as it can enable diagnosis even in the absence of specific clinical findings other than short stature, and guide the necessity, efficacy, and appropriate dosing of growth hormone therapy.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786092","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}