Molecular Syndromology最新文献

{"title":"Detecting a Novel &lt;i&gt;NOTCH3&lt;/i&gt; Variant in Patients with Suspected CADASIL: A Single Center Study","authors":"Zeynep Selcan Şanli, Özlem Anlaş","doi":"10.1159/000534243","DOIUrl":"https://doi.org/10.1159/000534243","url":null,"abstract":"<b><i>Introduction:</i></b> Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of familial cerebral small vessel disease in adults and is caused by <i>NOTCH3</i> variants. Clinical manifestations of CADASIL include recurrent ischemic strokes, dementia, migraine or migraineous headaches, epileptic seizures, and psychiatric disorders. The clinical-radiological phenotype of the disease is also highly variable. In this study, we investigated the variability of clinical, radiological, and genetic data in patients analyzed for <i>NOTCH3</i> variant in our clinic. <b><i>Methods:</i></b> We performed clinical and neuropsychological examination, cerebral magnetic resonance imaging (MRI) and Doppler sonography of cerebral arteries in all patients. Next-generation sequencing test was used for detect variants in <i>NOTCH3</i> gene from all CADASIL patients. <b><i>Results:</i></b> By using the next-generation sequencing method, heterozygous c.380C&amp;gt;T pathogenic variant was detected in the 4th exon of the <i>NOTCH3</i> gene in 3 patients. This is a previously unreported novel variant and resulted in the replacement of the amino acid Proline at 127th position with Leucine. <b><i>Discussion and Conclusion:</i></b> The discovery of this novel pathogenic variant region may contribute to the expansion of the clinical and genetic spectrum of diseases associated with NOTCH3, leading to further research and treatment options for this disease in the future.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"25 11","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135567337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Diagnosis of Limb-Girdle Muscular Dystrophy Using Next-Generation Sequencing Panels","authors":"Gamze Sarıkaya Uzan, Ceren Yılmaz Uzman, Tayfun Çinleti, Çağatay Günay, Ayfer Ülgenalp, Semra Hiz Kurul, Uluç Yiş","doi":"10.1159/000533976","DOIUrl":"https://doi.org/10.1159/000533976","url":null,"abstract":"<b><i>Introduction:</i></b> Limb-girdle muscular dystrophies (LGMDs) are clinically and genetically heterogeneous muscle disorders. We aimed to share the diagnostic yield of an NGS gene panel containing LGMD-related genes and our experience with LGMD. <b><i>Methods:</i></b> Between February 2019 and October 2022, patients with a suspicion of LGMD and their relatives were reviewed in terms of demographic, clinical, and individual genetic data, age of symptom onset, sex, clinical features, LGMD types, cardiac involvement, muscle biopsy results, family history, and consanguinity. Our NGS gene panel consisted of <i>ANO5, CAPN3, CAV3, DAG1, DES, DNAJB6, DYSF, FKTN, FLNC, FRKP, GAA, GMPPB, HNRNPDL, ISPD, LIMS2, LMNA, MYOT, PLEC, POMGNT1, POMK, POMT1, POMT2, SGCA, SGCB, SGCD, SGCG, TCAP, TNPO3, TRAPPC11, TRIM32,</i> and <i>TTN</i> genes. <b><i>Results:</i></b> The diagnosis rate was 61.1% (11/18). Twelve (80%) patients with LGMD were male and three (20%) were female. The median age was 15.9 (range, 1.5–39) years. Our patient collective was drawn up out of patients with the following variants: LGMDR1 (<i>n</i> = 6; 40%), LGMDR2 (<i>n</i> = 4; 26.6%), LGMDR3 (<i>n</i> = 4; 26.6%), and LGMDR12 (<i>n</i> = 1; 6.7%). <b><i>Conclusion:</i></b> The present study showed that the NGS panel has a high success rate in the diagnosis of LGMD and contributes to early diagnosis.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136078830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"&lt;i&gt;TPP1&lt;/i&gt; Variants in Iranian patients: A Novel Pathogenic Homozygous Variant Causing Neuronal Ceroid Lipofuscinosis 2","authors":"Nahid Vafaei, Ali Mohebbi, Zahra Rezaei, Morteza Heidari, Sareh Hosseinpour, Ali Zare Dehnavi, Azin Ghamari, Masoud Salehipour, Ali Rabbani, Nejat Mahdieh, Mahmoud Reza Ashrafi","doi":"10.1159/000534100","DOIUrl":"https://doi.org/10.1159/000534100","url":null,"abstract":"<b><i>Introduction:</i></b> <i>TPP1</i> variants have been identified as a causative agent of neuronal ceroid lipofuscinosis 2 disease, that ataxia is one of its clinical features. Therefore, here, molecular study of <i>TPP1</i> variants is presented in an Iranian cohort and a novel pathogenic variant is described. <b><i>Methods:</i></b> This investigation was conducted as a cross-sectional study in a tertiary referral hospital, Children’s Medical Center, Pediatrics Center of Excellence. Clinical presentations and pedigrees were documented. Patients with cerebellar ataxia were enrolled in this study. Next-generation sequencing was applied to confirm the diagnosis. Segregation and bioinformatics analyses were also done for the variants using Sanger sequencing. <b><i>Results:</i></b> Forty-five patients were included in our study. The mean age of onset was 104 (+55.60) months (minimum = 31 months, maximum = 216 months). The majority of cases (73.3%) were born to consanguineous parents and only 1 patient (2.2%) had an affected sibling. Of the 45 patients, only 1 patient with a novel pathogenic variant (c.1425_1425+1delinsAT, p.A476Cfs*15) in the <i>TPP1</i> gene was identified. <b><i>Discussion:</i></b> The main strength of current study is the relatively large sample size. Besides, a novel pathogenic variant could be important toward the diagnosis and management of this condition. With significant advances in various therapies, early diagnosis could improve the treatments using personalized-based medicine.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136078657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of &lt;i&gt;ABCA13&lt;/i&gt; Gene Variants with Autism Spectrum Disorder and Other Neuropsychiatric Disorders","authors":"Hamide Betul Gerik-Celebi, Gul Unsel-Bolat, Hilmi Bolat","doi":"10.1159/000534123","DOIUrl":"https://doi.org/10.1159/000534123","url":null,"abstract":"<b><i>Introduction:</i></b> Autism spectrum disorder (ASD) is a neuropsychiatric disorder characterized by impaired social skills and limited or repetitive behaviors. In this study, we investigated the role of the <i>ABCA13</i> gene in the etiopathogenesis of ASD. <b><i>Methods:</i></b> Single-nucleotide variants were evaluated in 79 ASD patients (59 males +20 females) with no established genetic etiology associated with ASD using whole-exome sequencing/clinical exome sequencing method. Family segregation analysis was performed using Sanger sequencing. We presented the clinical and genetic findings of these cases and their parents in detail. <b><i>Results:</i></b> We presented 10 different <i>ABCA13</i> gene variants in cases with ASD and 10 parents carrying the same <i>ABCA13</i> gene variant. There of these variants were likely pathogenic and seven variants were classified as variant of uncertain significance. Our cases had a comorbidity rate for attention deficit hyperactivity disorder (ADHD) as 70%. Various types of neuropsychiatric symptoms and diagnoses were detected including ADHD, anxiety disorder, intellectual disability, delay in speech, and febrile convulsion among the parents. <b><i>Conclusion:</i></b> To date, very few variants have been reported in the <i>ABCA13</i> gene. Our findings enrich the role of <i>ABCA13</i> gene may play a common role in the landscape of neuropsychiatric disorders.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136078658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Deeper Insight into &lt;i&gt;COL4A3&lt;/i&gt;, &lt;i&gt;COL4A4&lt;/i&gt;, and &lt;i&gt;COL4A5 &lt;/i&gt;Variants and Genotype-Phenotype Correlation of a Turkish Cohort with Alport Syndrome","authors":"Cüneyd Yavaş, Nehir Ozdemir Ozgenturk, Mustafa Dogan, Alper Gezdirici, Ece Keskin, Ezgi Gokpınar İli, Tunay Dogan, Evrim Celebi, Onur Bender, Cemal Un","doi":"10.1159/000533915","DOIUrl":"https://doi.org/10.1159/000533915","url":null,"abstract":"<b><i>Introduction:</i></b> Alport syndrome (AS) is an inherited, rare, progressive kidney disease that affects the eye and ear physiology. Pathogenic variants of <i>COL4A5</i> account for 85% of all cases, while <i>COL4A3</i> and <i>COL4A4</i> account for the remaining 15%. <b><i>Methods:</i></b> Targeted next-generation sequencing of the <i>COL4A3</i>, <i>COL4A4</i>, and <i>COL4A5</i> genes was performed in 125 Turkish patients with AS. The patients were compared to 45 controls and open-access population data. <b><i>Results:</i></b> The incidence of AS variants in patients was found as 21.6%. 27 variants were identified as pathogenic/likely pathogenic, 28 as variant of uncertain significance, and 52 as benign/likely benign. We also found 31 novel variants (14 in <i>COL4A3</i>, 6 in <i>COL4A4</i>, and 11 in <i>COL4A5</i>) of which 27 were classified as pathogenic/likely pathogenic. Pathogenic/likely Pathogenic variants were most commonly found in the <i>COL4A5</i> gene, consistent with the literature. This study contributed novel variants associated with AS to the literature. <b><i>Conclusion:</i></b> Genetic testing is a crucial part for the diagnosis and management of AS. Studies on the genetic etiology of AS are limited for the Turkish population. We believe that this study will contribute to the literature and the clinical decision-making process of patients with AS and emphasize the importance of genetic counseling.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136078664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Rare Presentation of Homozygous Pathogenic Variant in &lt;i&gt;MC2R&lt;/i&gt; Gene with Salt-Wasting Crisis in a Neonate","authors":"Aysenur Kardas Yildiz, Ali Bulbul, Buse Ozer Bekmez, Ayberk Turkyilmaz, Kerem Terali, Aydilek Dagdeviren Cakir, Ahmet Ucar","doi":"10.1159/000533986","DOIUrl":"https://doi.org/10.1159/000533986","url":null,"abstract":"<b><i>Introduction:</i></b> Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease resulting from isolated glucocorticoid deficiency or unresponsiveness to adrenocorticotropic hormone. Patients with FGD usually present in infancy or early childhood with hyperpigmentation, recurrent infections, and hypoglycemia. The salt-wasting crisis is rare. <b><i>Case Presentation:</i></b> A term female neonate was admitted to the neonatal intensive care unit due to respiratory distress. On physical examination, she had generalized hyperpigmentation. Initial laboratory work-up yielded normal serum electrolytes and glucose. Hyponatremia and hyperkalemia emerged on follow-up. The patient was diagnosed as having primary adrenal insufficiency (PAI) with elevated plasma adrenocorticotropin hormone and reduced cortisol levels and hydrocortisone. We started on oral sodium (5 mEq/kg/day) and fludrocortisone (FC) (0.2 mg/day) treatment to the patient. Ultrasonography revealed hypoplastic adrenal glands. Molecular genetic analysis revealed a previously reported homozygous pathogenic variant NM_000529.2: c.560delT (p.V187fs*29) in the <i>MC2R</i> gene. FC dose was tapered to 0.05 mg/day on the third month of life and was stopped at tenth months of age with maintenance of normal serum electrolytes and clinical findings. <b><i>Conclusion:</i></b> FGD due to <i>MC2R</i> gene mutation may rarely present with a salt-wasting crisis in the neonatal period. Identifying the causative gene with the pathogenic variant in PAI may serve to individualize a treatment plan.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135901537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Heterogeneity in Patients with Long QT Syndrome and Segregation of Single Nucleotide Variants and Clinical Symptoms in 17 Affected Families.","authors":"Elcin Bora, Ayca Yıldız Bulut, Tufan Cankaya, Tayfun Cinleti, Halise Zeynep Genç, Emin Evren Ozcan, Ebru Ozpelit, Ayfer Ulgenalp, Ahmet Okay Caglayan","doi":"10.1159/000530513","DOIUrl":"10.1159/000530513","url":null,"abstract":"<p><strong>Introduction: </strong>Long QT syndrome (LQTS) is a disorder of ventricular myocardial repolarization characterized by a prolonged QT interval on the electrocardiogram. It increases the risk of ventricular arrhythmias, which can cause syncope or sudden cardiac death. In this study, we study the genotype-phenotype relationships of patients referred to us with suspected arrhythmia syndrome.</p><p><strong>Methods: </strong>Seventeen cases and their twenty relatives were evaluated. Next-generation sequencing analysis was performed for 17 LQTS-related genes.</p><p><strong>Results: </strong>We detected seventeen single nucleotide variants (SNVs) with potential pathogenic significance in 26 of the 36 subjects analyzed. <i>KCNH2</i> c.172G>A, <i>KCNQ1</i> c.1768G>A, <i>ANK2</i> c.4666A>T, c.1484_1485delCT, <i>KCNH2</i> c.1888G>A were reported as pathogenic or likely pathogenic in HGMD variant classification database.</p><p><strong>Conclusion: </strong>Current study pointed out that early diagnosis can be life-saving for patients and their families by taking family history and detailed examination. Also, we highlight the clinical heterogeneity of arrhythmia syndrome through a patient with a dual phenotype.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 5","pages":"363-374"},"PeriodicalIF":1.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414853","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":"Autism Spectrum Disorder in Two Unrelated Patients with Homozygous Variants in Either ALG8 or ALG11.","authors":"Gozde Uzunyayla-Inci, Ertugrul Kiykim, Tanyel Zubarioglu, Gozde Yesil, Cigdem Aktuglu Zeybek","doi":"10.1159/000530118","DOIUrl":"10.1159/000530118","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is used to describe individuals with a specific combination of disorders in social communication and repetitive behaviors, highly restricted interests, and/or sensory behavior that begin early in life. The prevalence of ASD has been increasing rapidly in recent years. Pathophysiology of ASDs remains still unclear; however, genetic defects and multifactorial causes have been reported to play an important role in genetic disorders. The prevalence of inborn errors of metabolism (IEM) reported among patients with ASD is 2-5%. The clinical presentation of congenital disorders of glycosylation (CDG) may be in the form of psychiatric disorder only.</p><p><strong>Case study: </strong>Case 1: a 5-year-old female patient was admitted for investigation of ASD. She had a dysmorphic facial appearance, inverted nipples, abnormal fat distribution, ataxic gait, and autistic features. Her transferrin isoelectric focusing test was compatible with a type 1 CDG pattern. A homozygous variant in ALG8 gene revealed the diagnosis of ALG8-CDG (CDG Type 1H). Case 2: a 2-year-old male patient was admitted with complaints of ASD for investigation of an underlying IEM due to speech delay. Physical examination revealed hypertelorism, small hands, and autistic behavior. Transferrin isoelectric focusing test was also found normal. As a result of the WES, a homozygous variant was detected in ALG11 confirming the diagnosis of CDG type 1p.</p><p><strong>Conclusion: </strong>CDG should also be considered in the differential diagnosis of autistic patients with dysmorphic findings. The aim of our study was to emphasize that autism should be listed among the neurological findings of CDG.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 1","pages":"428-432"},"PeriodicalIF":0.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44721142","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>VAMP2</i> Gene-Related Neurodevelopmental Disorder: A Differential Diagnosis for Rett/Angelman-Type Spectrum of Disorders.","authors":"Danielle Bogue, Gavin Ryan, Evangeline Wassmer, Genomics England Research Consortium, Swati Naik","doi":"10.1159/000530150","DOIUrl":"10.1159/000530150","url":null,"abstract":"<p><strong>Introduction: </strong><i>VAMP2</i> is an instrumental protein in neuronal synaptic transmission in the brain, facilitating neurotransmitter release. It is encoded by the <i>VAMP2</i> gene, and pathogenic variants in this gene cause neurodevelopmental features including early onset axial hypotonia, intellectual disability, and features of autism spectrum disorder. To date, only three types of allelic variants (loss of function, in-frame deletions, and missense variants) in the <i>VAMP2</i> gene have been previously reported in 11 patients with learning difficulties. Here, we describe a patient in whom a novel de novo pathogenic variant in the <i>VAMP2</i> gene was identified.</p><p><strong>Case presentation: </strong>A 15-month-old girl presented with early onset hypotonia, global developmental delay, learning difficulties, microcephaly, nystagmus, strabismus, and stereotypies. Later, she developed a sleep disorder, challenging behaviour with self-injury, and scoliosis. Gene agnostic analysis of whole genome sequencing data identified a novel de novo heterozygous missense variant c.197G>C (p.Arg66Pro) in the <i>VAMP2</i> gene SNARE motif region.</p><p><strong>Discussion: </strong>This is the fourth report describing <i>VAMP2</i> gene-related neurodevelopmental disorder. This report adds to the genotype-phenotype correlation and highlights this condition as an important differential diagnosis of Rett/Angelman-type spectrum of disorders. Patients presenting with features of either Rett syndrome or Angelman syndrome, in whom genetic testing is not suggestive, should be evaluated for variants in the <i>VAMP2</i> gene, given the significant overlap in clinical presentation of these disorders.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 1","pages":"449-456"},"PeriodicalIF":1.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44986424","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":"Genotype and Phenotype Characterization of Patients with Mucopolysaccharidosis IV-A in Chile.","authors":"José Miguel Cárdenas, Diane Vergara, Scarlet Witting, Fernanda Balut, Patricio Guerra, José Tomás Mesa, Sebastián Silva, Javiera Tello, Álvaro Retamales, Andrés Barrios, Fernando Pinto, Víctor Faundes, Mónica Troncoso","doi":"10.1159/000529807","DOIUrl":"10.1159/000529807","url":null,"abstract":"<p><strong>Introduction: </strong>Morquio syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an autosomal recessive disease caused by biallelic variants in the <i>GALNS</i> gene, encoding the lysosomal enzyme GalN6S, responsible for glycosaminoglycan keratan sulfate and chondroitin-6-sulfate degradation. Studies have shown that the degree of evolutionary and chemical divergence of missense variants in GalN6S when compared to ancestral amino acids is associated with the severity of the syndrome, suggesting a genotype-phenotype correlation. There is little information on Latin American patients with MPS IV-A that replicate these findings. This study aimed to characterize the phenotype and genotype from patients with MPS IV-A, who are under Enzyme Replacement Therapy at the Children's Neuropsychiatry Service of the Hospital Clínico San Borja Arriarán, Santiago, Chile, and to determine if there is any association between genotype and phenotype with those findings.</p><p><strong>Methods: </strong>Information was collected from medical charts, all patients went through a GalN6S enzymatic activity measurement in leukocytes from peripheral blood, and the <i>GALNS</i> gene was sequenced for all cases.</p><p><strong>Results: </strong>12 patients with MPS IV-A were recruited, all patients presented multisystem involvement, mostly skeletal, and 75% of cases underwent surgical interventions, and cervical arthrodesis was the most frequent procedure. In regards of the genotype, the two most frequent variants were c.319+2T>C (<i>n</i> = 10, 41.66%) and p.(Arg386Cys) (<i>n</i> = 8, 33.33%), the first one was previously described in 2018 in a patient from Chile [Bochernitsan et al., 2018].</p><p><strong>Conclusion: </strong>This is the first time that a genotype-phenotype correlation has been studied by analyzing the variants effect on the molecular structure of human GalN6S and the evolutionary conservation degree of affected residues in a cohort of patients in Chile. Albeit our work could not find statistically significant associations, we may infer that the evolutionary conservations of affected amino acids and the effect of variants on enzyme structure may play a main role. Further analyzes should consider a meta-analysis of published cases with genotype data and larger samples and include other variables that could provide more information. Finally, our data strongly suggest that variant c.319+2T>C could have a founder effect in Chilean patients with MPS IV-A.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 1","pages":"416-427"},"PeriodicalIF":1.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47375988","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}