Molecular Syndromology最新文献

{"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}

{"title":"Reanalysis of Chromosomal Microarray Data Using a Smaller Copy Number Variant Call Threshold Identifies Four Cases with Heterozygous Multiexon Deletions of ARID1B, EHMT1, and FOXP1 Genes.","authors":"Noriko Kubota, Ryojun Takeda, Jun Kobayashi, Eiko Hidaka, Eriko Nishi, Kyoko Takano, Keiko Wakui","doi":"10.1159/000530252","DOIUrl":"10.1159/000530252","url":null,"abstract":"<p><strong>Introduction: </strong>Chromosomal microarray (CMA) is a highly accurate and established method for detecting copy number variations (CNVs) in clinical genetic testing. CNVs are important etiological factors for disorders such as intellectual disability, developmental delay, and multiple congenital anomalies. Recently developed analytical methods have facilitated the identification of smaller CNVs. Therefore, reanalyzing CMA data using a smaller CNV calling threshold may yield useful information. However, this method was left to the discretion of each institution.</p><p><strong>Methods: </strong>We reanalyzed the CMA data of 131 patients using a smaller CNV call threshold: 50 kb 50 probes for gain and 25 kb 25 probes for loss. We interpreted the reanalyzed CNVs based on the most recently available information. In the reanalysis, we filtered the data using the Clinical Genome Resource dosage sensitivity gene list as an index to quickly and efficiently check morbid genes.</p><p><strong>Results: </strong>The number of copy number loss was approximately 20 times greater, and copy number gain was approximately three times greater compared to those in the previous analysis. We detected new likely pathogenic CNVs in four participants: a 236.5 kb loss within <i>ARID1B</i>, a 50.6 kb loss including <i>EHMT1</i>, a 46.5 kb loss including <i>EHMT1</i>, and an 89.1 kb loss within the <i>FOXP1</i> gene.</p><p><strong>Conclusion: </strong>The method employed in this study is simple and effective for CMA data reanalysis using a smaller CNV call threshold. Thus, this method is efficient for both ongoing and repeated analyses. This study may stimulate further discussion of reanalysis methodology in clinical laboratories.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 1","pages":"394-404"},"PeriodicalIF":1.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42080086","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":"Extensive, 3.8 Mb-Sized Deletion of 22q12 in a Patient with Bilateral Schwannoma, Intellectual Disability, Sensorineural Hearing Loss, and Epilepsy.","authors":"Jakub Trizuljak, Jakub Duben, Ivona Blaháková, Zuzana Vrzalová, Kateřina Staňo Kozubík, Jiří Štika, Lenka Radová, Veronika Bergerová, Soňa Mejstříková, Věra Hořínová, Radim Jančálek, Šárka Pospíšilová, Michael Doubek","doi":"10.1159/000528744","DOIUrl":"10.1159/000528744","url":null,"abstract":"<p><strong>Introduction: </strong>In contrast with the well-known and described deletion of the 22q11 chromosome region responsible for DiGeorge syndrome, 22q12 deletions are much rarer. Only a few dozen cases have been reported so far. This region contains genes responsible for cell cycle control, chromatin modification, transmembrane signaling, cell adhesion, and neural development, as well as several cancer predisposition genes.</p><p><strong>Case presentation: </strong>We present a patient with cleft palate, sensorineural hearing loss, vestibular dysfunction, epilepsy, mild to moderate intellectual disability, divergent strabism, pes equinovarus, platyspondylia, and bilateral schwannoma. Using Microarray-based Comparative Genomic Hybridization (aCGH), we identified the de novo 3.8 Mb interstitial deletion at 22q12.1→22q12.3. We confirmed deletion of the critical <i>NF2</i> region by MLPA analysis.</p><p><strong>Discussion: </strong>Large 22q12 deletion in the proband encases the critical <i>NF2</i> region, responsible for development of bilateral schwannoma. We compared the phenotype of the patient with previously reported cases. Interestingly, our patient developed cleft palate even without deletion of the <i>MN1</i> gene, deemed responsible in previous studies. We also strongly suspect the <i>DEPDC5</i> gene deletion to be responsible for seizures, consistent with previously reported cases.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 5","pages":"439-448"},"PeriodicalIF":1.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427986","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":"Novel <i>SYNGAP1</i> Variant in an Adult Individual Affected by Intellectual Disability and Epilepsy: A Cold Case Solved through Whole-Exome Sequencing.","authors":"Giulia Rosti, Silvia Boeri, Maria Teresa Divizia, Livia Pisciotta, Maria Margherita Mancardi, Margherita Lerone, Maria Cerminara, Martina Servetti, Giovanni Spirito, Diego Vozzi, Marco Fontana, Stefano Gustincich, Lino Nobili, Federico Zara, Aldamaria Puliti","doi":"10.1159/000529408","DOIUrl":"10.1159/000529408","url":null,"abstract":"<p><strong>Introduction: </strong>Nowadays, whole-exome sequencing (WES) analysis is an essential part in the diagnostic pathway of individuals with complex phenotypes when routine exams, such as array-CGH and gene panels, have proved inconclusive. However, data on the diagnostic rate of WES analysis in adult individuals, negative to first-tier tests, are lacking. This is because initiatives with the aim of diagnosing rare diseases focus mainly on pediatric unsolved cases.</p><p><strong>Case presentation: </strong>We hereby present a 45-year-old woman with severe intellectual disability, previous psychomotor developmental delay, behavioral disorders, stereotypies, nonconvulsive epilepsy, and dysmorphisms. The proband first came to our attention when she was 4 years old (in 1982); since then, she has undergone several clinical and instrumental assessments, without reaching a genetic diagnosis. At last, through WES analysis, a novel de novo variant in <i>SYNGAP1</i> was found. The clinical characteristics associated with <i>SYNGAP1</i> are similar to those presented by the proband.</p><p><strong>Conclusion: </strong>The variant is predicted to be deleterious and is most probably the cause of the proband's phenotype. The perseverance of the clinicians and the family allowed us to reach a diagnosis in a woman with a more than 30-year history of clinical evaluations, instrumental assessments, and genetic tests. This diagnosis was of significant relevance in genetic counseling for family members and the proband herself.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 5","pages":"433-438"},"PeriodicalIF":1.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427987","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}