{"title":"The Clinical and Molecular Spectrum of Patients With X-Linked Intellectual Disability and Novel Variations in Different Genes","authors":"Semra Gürsoy MD , Ceren Yılmaz Uzman MD , Kadri Murat Erdoğan MD , Pakize Karaoğlu MD , Tuba Sözen Türk MD , Ünsal Yılmaz MD , Aycan Ünalp MD , Filiz Hazan MD","doi":"10.1016/j.pediatrneurol.2025.01.016","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. In this study, we aimed to describe the clinical and molecular spectrum of patients with XLID. We also evaluated the clinical efficacy of a targeted gene panel in patients with suspected XLID.</div></div><div><h3>Methods</h3><div>Eighty-four patients with suspected XLID were enrolled in the study. Array comparative genomic hybridization, fragile X fragman analysis, and targeted XLID gene panel were performed.</div></div><div><h3>Results</h3><div>Genetic diagnosis was established in a total of 24 patients (22 male and two female) with XLID. Different copy number variations of the X chromosome were detected in four patients, including two duplications and two deletions. Fifteen patients had fragile X syndrome. Point mutations were detected in five unrelated patients. Variants detected in <em>RPS6KA3</em> gene were previously reported by our team. A novel two-nucleotide deletion was shown in the <em>MID1</em> gene. Additionally, novel missense variations were revealed in <em>IL1RAPL1</em> and <em>ATRX</em> genes. The <em>IL1RAPL1</em> variant was detected in additional five affected male patients in the same family. The patient, who had <em>ATRX</em> variation, had pachygyria in the cerebral cortex and hypoplasia of cerebellar vermis.</div></div><div><h3>Conclusions</h3><div>Our findings have broadened the spectrum of mutations and clinical manifestations of patients with XLID. Additionally, this represents the second reported missense variation in the <em>IL1RAPL1</em> gene identified in patients with XLID. We also emphasized the importance of a stepwise diagnostic algorithm that incorporates chromosomal microarray analysis, <em>FMR1</em> gene repeat analysis, and next-generation sequencing analysis for patients with XLID.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"165 ","pages":"Pages 43-51"},"PeriodicalIF":3.2000,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric neurology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0887899425000244","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. In this study, we aimed to describe the clinical and molecular spectrum of patients with XLID. We also evaluated the clinical efficacy of a targeted gene panel in patients with suspected XLID.
Methods
Eighty-four patients with suspected XLID were enrolled in the study. Array comparative genomic hybridization, fragile X fragman analysis, and targeted XLID gene panel were performed.
Results
Genetic diagnosis was established in a total of 24 patients (22 male and two female) with XLID. Different copy number variations of the X chromosome were detected in four patients, including two duplications and two deletions. Fifteen patients had fragile X syndrome. Point mutations were detected in five unrelated patients. Variants detected in RPS6KA3 gene were previously reported by our team. A novel two-nucleotide deletion was shown in the MID1 gene. Additionally, novel missense variations were revealed in IL1RAPL1 and ATRX genes. The IL1RAPL1 variant was detected in additional five affected male patients in the same family. The patient, who had ATRX variation, had pachygyria in the cerebral cortex and hypoplasia of cerebellar vermis.
Conclusions
Our findings have broadened the spectrum of mutations and clinical manifestations of patients with XLID. Additionally, this represents the second reported missense variation in the IL1RAPL1 gene identified in patients with XLID. We also emphasized the importance of a stepwise diagnostic algorithm that incorporates chromosomal microarray analysis, FMR1 gene repeat analysis, and next-generation sequencing analysis for patients with XLID.
期刊介绍:
Pediatric Neurology publishes timely peer-reviewed clinical and research articles covering all aspects of the developing nervous system.
Pediatric Neurology features up-to-the-minute publication of the latest advances in the diagnosis, management, and treatment of pediatric neurologic disorders. The journal''s editor, E. Steve Roach, in conjunction with the team of Associate Editors, heads an internationally recognized editorial board, ensuring the most authoritative and extensive coverage of the field. Among the topics covered are: epilepsy, mitochondrial diseases, congenital malformations, chromosomopathies, peripheral neuropathies, perinatal and childhood stroke, cerebral palsy, as well as other diseases affecting the developing nervous system.