Molecular Syndromology最新文献

{"title":"Erratum.","authors":"","doi":"10.1159/000545707","DOIUrl":"https://doi.org/10.1159/000545707","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1159/000543315.].</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"1"},"PeriodicalIF":0.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035316","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 <i>GATAD2B</i> Frameshift Variant Causes GATAD2B-Associated Neurodevelopmental Disorder with Camptodactyly.","authors":"Cheryl Weiqi Tan, Jiin Ying Lim, Khadijah Rafi'ee, Jeannette Goh, Chew Thye Choong, Sing Ming Chao, Benjamin Chang, Saumya S Jamuar, Ene-Choo Tan","doi":"10.1159/000545445","DOIUrl":"https://doi.org/10.1159/000545445","url":null,"abstract":"<p><strong>Introduction: </strong>GATAD2B-associated neurodevelopmental disorder (GAND) is caused by pathogenic variants in <i>GATAD2B</i> which encodes p66beta, a subunit of a transcription repressor. The main presentations of GAND are intellectual disability, speech impairment, and dysmorphism. However, these features overlap with other neurodevelopmental syndromes and are not specific enough to be recognised for a particular clinical diagnosis without molecular confirmation.</p><p><strong>Methods: </strong>Macrocephaly was detected prenatally and at birth. Postnatal brain MRI also revealed ventriculomegaly. Chromosomal microarray analysis and metabolites in plasma, serum, or urine were investigated due to microcephaly and dysmorphism, and all results were normal. Next-generation sequencing using a targeted gene panel did not identify any pathogenic variant. Exome sequencing was subsequently performed.</p><p><strong>Results: </strong>A heterozygous single nucleotide deletion in exon 5 of <i>GATAD2B</i> (p.His216Metfs*24) was detected and Sanger validated. Targeted Sanger sequencing of parental samples showed that it is de novo.</p><p><strong>Conclusion: </strong>We describe the first patient with GAND from Southeast Asia with Korean-Chinese parentage. The identification of a pathogenic variant in <i>GATAD2B</i> clarifies her diagnosis and adds to the genotypic and phenotypic spectrum of this disorder. This report illustrates the use of genetic testing to obtain a definite diagnosis.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"1-5"},"PeriodicalIF":0.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081425","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":"Focal Dermal Hypoplasia with Unusual Cardiac Anomalies Presentation: A Report of Two Cases and Literature Review.","authors":"Nagehan Bilgeç, Mahmut Gökdemir, Özgür Balasar, Fayize Maden Bedel, Hüseyin Çaksen","doi":"10.1159/000545533","DOIUrl":"10.1159/000545533","url":null,"abstract":"<p><strong>Introduction: </strong>Focal dermal hypoplasia (FDH), also known as Goltz syndrome, is an exceedingly rare multisystemic disease with X-linked dominant inheritance involving meso-ectodermal tissues. FDH is characterized by specific cutaneous lesions, ectodermal findings, craniofacial abnormalities, ocular malformations, and limb deformities. Congenital diaphragmatic hernia, urinary anomalies, heart anomalies, lung defects, or central nervous system malformations rarely accompany it.</p><p><strong>Case presentation: </strong>We report 2 patients with focal dermal hypoplasia with concurrent cardiac findings and <i>PORCN</i> variants. In the first case, hemitruncus, an aortic arch, severe isthmus hypoplasia, and pulmonary arterial hypertension were observed. In the second case, a secundum-type atrial septal defect was observed.</p><p><strong>Conclusion: </strong>Genotype-phenotype correlations are limited in the literature. We aimed to establish the genotype-phenotype relationship of the novel variants detected and better understand the correlation between the clinical features of focal dermal hypoplasia and the Wnt signaling mechanism.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"1-13"},"PeriodicalIF":0.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144100","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 Loss of Function Variant in <i>HCN1</i> Gene Underlies Early Infantile Epileptic Encephalopathy 24 [EIEE24].","authors":"Mujahid, Ahmed Waqas, Ibrahim A Almazni, Gohar Zaman, Qamre Alam, Thamir M Eid, Mohammad A Alanazi, Abdullah Hamadi, Tayyaba Afsar, Suhail Razak, Muhammad Umair","doi":"10.1159/000541117","DOIUrl":"10.1159/000541117","url":null,"abstract":"<p><strong>Background: </strong>Early infantile epileptic encephalopathy (EIEE) is a rare neurological condition characterized by frequent seizures in the early stages of life, resulting in severely impaired cognitive and motor development. Although the specific causes of EIEE remain unknown, one of the primary causes is gene pathogenicity (even in the absence of consanguinity). Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) are essential for proper brain function. They are regulated by multiple genes, and mutations in these genes induce channel malfunction, which can result in various severe conditions, including EIEE. Herein, we have reported a patient presenting hallmarks of EIEE.</p><p><strong>Methods: </strong>The patient underwent clinical, radiographic, and genetic analysis. A thorough clinical examination and molecular study were conducted utilizing whole exome sequencing and Sanger sequencing.</p><p><strong>Results: </strong>Whole exome sequencing of the proband revealed a novel de novo nonsynonymous/nonsense variant (c.1468A>T; (p.Lys490Ter) in exon 6 of the <i>HCN1</i> gene. This variant may cause channel dysfunction via nonsynonymous/nonsense-mediated decay or aberrant protein, which may be associated with EIEE phenotypes.</p><p><strong>Conclusions: </strong>This evidence backs the idea that HCN1 has a vital role in brain development and lose of function can cause a range of debilitating conditions. Still, the functional characterization study of the <i>HCN1</i> variants will be the fundamental tool for a better understanding of EIEE in the near future.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"16 2","pages":"152-164"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774484","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":"Clinical and Radiological Profile of Nine Patients with Metachromatic Leukodystrophy.","authors":"Çiğdem Seher Kasapkara, Burcu Civelek Ürey, Berrak Bilginer Gürbüz, Aynur Küçükçongar Yavaş, Avni Merter Keçeli, Ümmühan Öncül, Mehmet Gündüz, Gürsel Biberoğlu, Ayşegül Neşe Çıtak Kurt, Esra Gürkaş, Esra Kılıç, Gülay Güleç Ceylan, Namık Yaşar Özbek","doi":"10.1159/000540925","DOIUrl":"10.1159/000540925","url":null,"abstract":"<p><strong>Introduction: </strong>Metachromatic leukodystrophy (MLD) is a rare, demyelinating, autosomal recessive lysosomal storage disease caused by a deficiency in the arylsulfatase A enzyme (ASA), which is encoded by <i>ARSA</i> gene. A lack of ASA activity results in an accumulation of sulfatides in the myelin sheaths of both the central and peripheral nervous systems, leading to developmental and neurocognitive progressive deterioration that can be observed in all age groups.</p><p><strong>Methods: </strong>We present a total of 9 patients with MLD with an average age of 61 months, whose clinical, laboratory and cranial magnetic resonance imaging findings were evaluated, and who underwent an <i>ARSA</i> gene molecular analysis.</p><p><strong>Results: </strong>Of the 9 patients, 7 had the late infantile form of the condition, 2 had the juvenile form, and 3 were identified through family screening. The median age at diagnosis was 30 months (min 3-max 73 months), the mean ASA activity value was 2 nmol/h/mgprt and the median cranial MR imaging severity score was 10 (min 5-max 18). The grey and white matter volumes of all patients, evaluated using volBrain software, were within the normal range. At an average age of 48 months, the late-infantile MLD patients were unable to control any body part.</p><p><strong>Conclusions: </strong>Hematopoietic stem cell transplantation (HSCT), a treatment option for both the juvenile and adult forms of MLD in asymptomatic or early symptomatic patients, was performed on two of the asymptomatic and early symptomatic patients, and post-HSCT ASA activity settled within the normal range and their developmental milestones stabilized. It is important to diagnose MLD in the asymptomatic period and newborn screening can support early diagnosis.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"16 2","pages":"138-151"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774558","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 New Case with Weaver Syndrome: Delineating Natural Course and Growth Pattern, Further Clarifying Clinical Phenotype.","authors":"Yağmur Ünsal, Nalan Yıldırım, Ayşe Derya Buluş, Esra Kılıç","doi":"10.1159/000541476","DOIUrl":"10.1159/000541476","url":null,"abstract":"<p><strong>Introduction: </strong>Weaver syndrome, rare syndromic cause of tall stature, presents with overgrowth, accelerated skeletal maturation, dysmorphic features, and camptodactly. Despite expanding knowledge and widespread use of genetic tests, differential diagnosis of tall statue may be challenging, complicating follow-up. Here we describe a patient with a variant in <i>EZH2</i>, underlining presenting features and natural course.</p><p><strong>Case presentation: </strong>Twenty-month-old girl consulted for tall stature was born at term (birthweight: 2,600 g [-0.8 SDS], birth length: 54 cm [2.4 SDS]) as the third child of non-consanguineous parents. Without any other complaints, she was 15.2 kg (2.5 SDS) and her height was 95 cm (3.1 SDS). She was proportionately tall compared to her parents (target height: 156 cm [-1.1 SDS]). Endocrine evaluation did not reveal pathology, growth traced parallel to 97th percentile of growth curve. Karyotype analysis and fibrillin gene analysis were normal. As she had mild intellectual disability and minor dysmorphic features (broad forehead, mild hypertelorism, long philtrum, thin upper lip and a prominent chin dimple, bilateral camptodactyly), whole exome analysis including copy number variant changes that revealed a heterozygous variant on <i>EZH2</i> was performed when she was 14 years old. Weaver syndrome was diagnosed.</p><p><strong>Conclusion: </strong>Tall stature, height SDS exceeding target height SDS, tall stature at birth, normal growth rate, minor dysmorphic features, and mild intellectual disability should prompt syndromic etiology of tall stature. Further genetic analysis should be implemented. Diagnosis of rare syndromes is crucial for defining prognosis, organ involvement, and natural course, avoiding unnecessary endocrine investigations.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"16 2","pages":"187-193"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774482","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":"Phenotypic Delineation of Combined Oxidative Phosphorylation Deficiency-12: Clinical Features of 2 Patients.","authors":"Meral Bahar Ister, Muge Cinar, Serdar Ceylaner, Ozlem Unal Uzun","doi":"10.1159/000541501","DOIUrl":"10.1159/000541501","url":null,"abstract":"<p><strong>Introduction: </strong>Combined oxidative phosphorylation deficiency-12 (COXPD12) is a rare autosomal recessive disorder. Neurological findings and lactic acidosis can be presenting signs of COXPD12.</p><p><strong>Case presentation: </strong>Here, we present identical dysmorphic facial features that have not been described before in the literature, in 2 patients with two different <i>EARS2</i> gene variants. Case 1 was a 2.5-month-old male who presented with hypotonia and lactic acidosis. Cranial magnetic resonance imaging (MRI) showed diffusion restriction in the supratentorial deep white matter, around the ventricle, in the bilateral periaqueductal gray matter at the level of the basal ganglia, and in the dentate nuclei in the tegmentum. Case 2 was a 2-month-old boy who also presented with lactic acidosis and hypotonia. Diffusion MRI reported hypomyelination. Dysmorphic facial features including slight metopic ridge, ptosis, wide palpebral fissure length, sparse eyebrows, bulbous nose, thin upper lip, full cheeks, small chin, large ears, thin ear helix, and prominent antihelix were common findings in both patients. Molecular genetic analysis indicated c.319C>T(p. Arg107Cys) common genetic variant in our 2 patients. In case 2, the second allele was a novel genetic variant.</p><p><strong>Conclusion: </strong>For COXPD12 disease, facial features are considered the main diagnostic clue, such as hypotonia or lactic acidosis; thus, the characteristic facial phenotype will help clinicians diagnose the disease.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"16 2","pages":"180-186"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773948","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 Patient with Organic Acidemia, Hyperammonemia, and a <i>FBXL4</i> Variant Suggesting Mitochondrial DNA Depletion Syndrome.","authors":"Merve Keser, Büşra Demirci, Habibe Koç Uçar, Özlem Akgün, İlknur Arslan, Berrak Bilginer Gürbüz","doi":"10.1159/000545585","DOIUrl":"https://doi.org/10.1159/000545585","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondrial DNA depletion syndromes encompass rare genetic disorders stemming from various gene defects, including encephalomyopathic mtDNA depletion syndrome 13 (MTDPS13), an autosomal recessive condition linked to <i>FBXL4</i> gene variants. Although its prevalence is estimated at 1/100,000-400,000, the mechanism behind MTDPS13 remains incompletely understood. Recent studies suggest <i>FBXL4</i> variants disrupt mitophagy, contributing to its pathogenesis.</p><p><strong>Case presentation: </strong>A 3-year and 4-month-old male presented with respiratory distress, diarrhea, and unconsciousness. His medical history revealed developmental delay and dysmorphic features. Physical examination unveiled characteristic dysmorphisms, while neurological assessment indicated abnormalities. Laboratory findings exhibited metabolic disturbances consistent with MTDPS13, confirmed by genetic analysis revealing a homozygous c.1555C>T <i>FBXL4</i> variant.</p><p><strong>Conclusion: </strong>FBXL4 defects, found in approximately 0.7% of suspected mitochondrial disease cases, lead to varied phenotypes with nonspecific facial dysmorphisms. The patient's presentation aligned with reported features, including growth delay, hypotonia, and developmental delay. Notably, the diagnosis occurred later than typical onset, highlighting the variability in disease manifestation. Treatment focused on symptom management, with dichloroacetic acid effectively addressing lactic acidosis. This case underscores the importance of considering mitochondrial diseases, particularly FBXL4-related MTDPS13, in patients presenting with metabolic disturbances and dysmorphic features. Early recognition facilitates appropriate management and genetic counseling for affected families.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"1-7"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043583","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":"Exploring the Genetic Etiology of Pediatric Epilepsy: Insights from Targeted Next-Generation Sequence Analysis.","authors":"Ozden Ozturk, Murat Ozturk, Kubra Ates, Zeynep Esener, Naile Nisa Erguven, Bilge Ozgor, Serdal Gungor, Ahmet Sigirci, Ibrahim Tekedereli","doi":"10.1159/000540762","DOIUrl":"10.1159/000540762","url":null,"abstract":"<p><strong>Introduction: </strong>Epilepsy is a group of neurologic disorders with clinical and genetic heterogeneity. Epilepsy often affects children; thus, early diagnosis and precise treatment are vital to protecting the standard of life of a child. Progress in epilepsy-related gene discovery has caused enormous novelty in specific epilepsy diagnoses. Genetic testing using next-generation sequencing is now reachable, leading to higher diagnosis ratios and understanding of the disease's underlying mechanisms. The study's primary aim was to identify the genetic etiology based on targeted next-generation sequence analysis data and to calculate the diagnostic value of the epilepsy gene panel in the 0-17 age-group diagnosed with epilepsy. The secondary aim was to demonstrate the significance of periodic reinterpretation of variant of uncertain significance (VUS) variants and genotype-phenotype correlation.</p><p><strong>Methods: </strong>This retrospective study comprised 107 patients with epilepsy aged 8 months to 17 years, for whom a targeted gene panel covered 110 genes. VUS variants were reanalyzed, and genotype-phenotype correlation was performed.</p><p><strong>Results: </strong>In the initial evaluation, causal variants were described in 23 patients (21.5%). After reinterpretation of VUS, we detected causal variants in 30 out of 107 patients (28%). By reinterpreting the VUS and evaluating genotype-phenotype correlations, we enhanced our diagnostic value by 30.32%. After reinterpretation of VUS variants, the ACMG classification of 36 variants, including 15 benign (31%), 15 likely benign (31%), 5 likely pathogenic (10%), and 1 pathogenic (2%), were redefined. We most frequently detected causal variants in <i>TSC2</i> (<i>n</i> = 5), <i>GRIN2A</i> (<i>n</i> = 4), and <i>ALDH7A1</i> (<i>n</i> = 4) genes.</p><p><strong>Conclusion: </strong>The predictive value for epilepsy panel testing was 28% in the cohort. Our study revealed the importance of reanalysis of VUS variants and contributed to enriching the mutation spectrum in epilepsy.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"16 2","pages":"115-127"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773651","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":"Classification of Brain Magnetic Resonance Imaging Abnormalities and Spectrum of Neurological Findings in a Cohort with Copy Number Variation-Related Disorders.","authors":"Ayberk Türkyılmaz, Safiye Güneş Sağer, Emine Caliskan, Merve Akçay, Oğuzhan Demir, Baran Baytar, Yasemin Akın","doi":"10.1159/000540599","DOIUrl":"10.1159/000540599","url":null,"abstract":"<p><strong>Introduction: </strong>Copy number variation (CNV) is the difference in the sequence of genomic segments, which can vary from one kilobase to several megabases. Certain CNVs have been linked to various human disorders, such as intellectual disability, multiple congenital anomalies, autism spectrum disorders, neurodegenerative and neuropsychiatric conditions, and cancer. The present study aims to classify brain magnetic resonance imaging (MRI) findings, describe neurological manifestations, and discuss the findings within the context of genotype-phenotype correlations in a cohort of patients with recurrent and nonrecurrent CNVs.</p><p><strong>Methods: </strong>A total of 21 patients with pathogenic CNV detected using microarray analysis were included in the study.</p><p><strong>Results: </strong>Analysis of the clinical findings of the patient cohort showed that 16 (76%) had microcephaly, 14 had epilepsy (66%), 20 had facial dysmorphism (95%), and all had developmental delay (100%). Novel brain MRI findings were detected in six (6/13, 46%) patients with recurrent CNV and five (5/8, 63%) patients with nonrecurrent CNV.</p><p><strong>Conclusion: </strong>CNV-related disorders should be considered in the differential diagnosis of patients with brain MRI findings suspicious for metabolic disorders. Brain MRI differences in patients with the same chromosomal deletion can be explained by the second-hit hypothesis. Additional single nucleotide variations and epigenetic factors in these cases may have led to the involvement of different regions of the brain. Revealing the phenotypic and genotypic characteristics of cases in rare disorders will contribute to the widespread use of precision medicine and genetic treatment approaches in the near future.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"16 2","pages":"99-114"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774544","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}