Molecular Syndromology最新文献

{"title":"Biallelic Deletion of <i>PEX26</i> Exon 4 in a Boy with Phenotypic Features of both Zellweger Syndrome and Infantile Refsum Disease.","authors":"Burhanettin Yalçınkaya, Kübra Adanur Sağlam, Kerem Terali, Emine Tekin, Hava Taslak, Ayberk Türkyılmaz","doi":"10.1159/000538676","DOIUrl":"10.1159/000538676","url":null,"abstract":"<p><strong>Introduction: </strong>Peroxisome biogenesis disorders (PBDs) encompass a group of diseases marked by clinical and genetic heterogeneity. Phenotypes linked to PBDs include Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease (IRD), rhizomelic chondrodysplasia punctata type 1, and Heimler syndrome. PBD phenotypes manifest through hypotonia, developmental delay, facial dysmorphism, seizures, liver dysfunction, sensorineural hearing loss, and retinal dystrophy.</p><p><strong>Methods: </strong>The proband underwent comprehensive clinical evaluation, followed by whole-exome sequencing (WES) coupled with copy number analysis (CNV), aimed at identifying potential disease-causing variants aligning with the observed phenotype.</p><p><strong>Results: </strong>Our findings detail an individual exhibiting developmental delay, hearing loss, visual impairment, hepatomegaly, and splenomegaly, attributed to a biallelic deletion of exon 4 in the <i>PEX26</i> gene. The WES analysis of the index case did not uncover any pathogenic/likely pathogenic single-nucleotide variations that could account for the observed clinical findings. However, the CNV data derived from WES revealed a homozygous deletion in exon 4 of the <i>PEX26</i> gene (NM_001127649.3), providing a plausible explanation for the patient's clinical features. The exon 4 region of <i>PEX26</i> encodes the transmembrane domain of the protein. The transmembrane domain plays a crucial role in anchoring the protein within lipid bilayers, and its absence can disrupt proper localization and functioning. As a result, this structural alteration may impact the protein's ability to facilitate essential cellular processes related to peroxisome biogenesis and function.</p><p><strong>Conclusion: </strong>The index patient, which presented with hearing loss, retinal involvement and hepatic dysfunction in adolescence age, has atypical clinical course that can be considered unusual for Zellweger syndrome (ZS) and IRD phenotypes, and its rare genotypic data (in-frame single exon deletion) expands the PBD disease spectrum. This study revealed for the first time that PEX26 protein transmembrane domain loss exhibits an unusual course with clinical findings of IRD and ZS phenotypes. WES studies, incorporating CNV analyses, empower the identification of novel genetic alterations in genes seldom associated with gross deletion/duplication variations, such as those in the <i>PEX26</i> gene. This not only enhances diagnostic rates in rare diseases but also contributes to broadening the spectrum of causal mutations.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"15 5","pages":"380-388"},"PeriodicalIF":0.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367059","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":"Is 5-Oxoprolinase Deficiency More than Just a Benign Condition?","authors":"Çiğdem Seher Kasapkara, Oya Kıreker Köylü, Ayşenur Engin Erdal, Burak Yürek, Nesrin Ceylan, Serdar Ceylaner","doi":"10.1159/000536295","DOIUrl":"10.1159/000536295","url":null,"abstract":"<p><strong>Introduction: </strong>Inherited 5-oxoprolinase (OPLAH) deficiency is a rare inborn condition characterized by 5-oxoprolinuria. The inherited condition of 5-oxoprolinuria, or pyroglutamic aciduria, is primarily caused by mutations in the genes that encode glutathione synthetase (GSS) and 5-oxoprolinase (OPLAH), which are enzymes involved in the gamma-glutamyl cycle in glutathione metabolism. We report a 3-year-old male patient with epilepsy and speech difficulty diagnosed as primary 5-oxoprolinuria due to a novel <i>OPLAH</i> gene mutation.</p><p><strong>Case presentation: </strong>A 3-year-old boy who was delivered at full term in an uncomplicated birth to consanguineous parents presented with epilepsy at the age of 2 years. He did not speak fluently. He was using 5-10 words with decreased language fluency. His past medical history revealed postnatal macrocephaly, hydrocephalus, and well-controlled epilepsy with levetiracetam. Progressive cerebral atrophy, hypomyelination, ventriculomegaly, and corpus callosum hypoplasia were striking features in brain MRI. A urine sample was sent for organic acid analysis by gas chromatography-mass spectrometry (GC-MS); quantitation of 5-oxoproline by stable isotope dilution gave a value of 177.9 mmol/mol creatinine (reference values 25.8-92.2). Molecular genetic analysis of the OPLAH gene revealed a novel homozygous variant (<i>OPLAH</i> (NM_017570.5): c.1909C>T p.Arg637Trp).</p><p><strong>Conclusion: </strong>We conclude that inherited 5-oxoprolinase deficiency is not a benign biochemical condition, and patients with 5-oxoprolinuria should be screened for it. The nature of this inherited metabolic disorder must be determined through long-term observation. We wish to emphasize the significance of molecular genetic analysis in symptomatic patients with persistently elevated levels of 5-oxoproline in the urine, as measured by organic acid analysis.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"15 4","pages":"303-310"},"PeriodicalIF":0.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917890","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 Molecular Characterization of Mucopolysaccharidosis Type 3A and 3B in a Turkish Series.","authors":"Bilge Noyan, Nursel H Elcioglu, Abdellah Tebani, Soumeya Bekri","doi":"10.1159/000535888","DOIUrl":"10.1159/000535888","url":null,"abstract":"<p><strong>Introduction: </strong>Sanfilippo syndrome or mucopolysaccharidosis type 3 (MPS-3) is a rare condition and its epidemiological data are still not defined. MPS-3 is linked to a deficiency in enzymes involved in heparan sulfate degradation. This biomolecule is neurotoxic and its accumulation underlies the severe central nervous system degeneration observed in this disease.</p><p><strong>Methods: </strong>Here, we describe 15 Turkish patients with MPS-3A or MPS-3B subtypes. Clinical data upon the diagnosis and during the follow-up as well as molecular characterization are reported.</p><p><strong>Results: </strong>Two and ten distinct variants were identified in <i>SGSH</i> and <i>NAGLU</i> gene sequences, respectively. Six variants (<i>NAGLU</i> NM_000263.3:c.532-?_c.764+?del, NAGLU NM_000263.3: c.509G>T, <i>NAGLU</i> NM_000263.3: c.700C>G, <i>NAGLU</i> NM_000263.3:c.507_516 del, <i>NAGLU</i> NM dises_000263.3: c.1354 G>A, <i>NAGLU</i> NM_000263.3: c.200T>C) have been previously published and 6 are novel (<i>SGSH</i> NM_000199.4: c.80T>G, <i>SGSH</i> NM_000199.4: c.7_16del, <i>NAGLU</i> NM_000263.3: c.224_235del, <i>NAGLU</i> NM_000263.3: c.904G>T, <i>NAGLU</i> NM_000263.3: c.626C>T, <i>NAGLU</i> NM_000263.3: c.1241A>G). <i>SGSH</i> NM_000199.4:c.7_16del variation might be caused by a founder effect.</p><p><strong>Conclusion: </strong>Due to the high rate of consanguinity in Turkey, the incidence of Sanfilippo syndrome might be higher compared to other populations worldwide. Our results contribute to the characterization of rare diseases in Turkey and to improve our knowledge of the clinical, molecular, and epidemiological aspects of MPS-3 disease.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"15 3","pages":"194-201"},"PeriodicalIF":1.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141263289","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 Long-Term Follow-Up of a Patient with a Novel PORCN Variant and Additional Clinical Features","authors":"Akçahan Akalın, K. Grzeschik, E. Utine, K. Boduroğlu, P. Simsek-Kiper","doi":"10.1159/000535681","DOIUrl":"https://doi.org/10.1159/000535681","url":null,"abstract":"Introduction: Focal dermal hypoplasia (FDH) is a genodermatosis also known as Goltz-Gorlin syndrome caused by pathogenic variants in the PORCN gene and inherited in an X-linked dominant manner. Given the course of X-linked dominant inheritance, affected males can only survive in the state of mosaicism for a PORCN pathogenic variant or in the presence of XXY karyotype. FDH is a multisystemic disorder in which cutaneous, ocular, and skeletal systems are primarily affected. Patients also may display intellectual disability and central nervous system abnormalities, yet most may have normal mental development. Case Presentation: We report on a currently 11-year-old female patient with a novel missense heterozygous PORCN variant who exhibited classical ectodermal, skeletal, and ocular findings in addition to mild intellectual disability, left-side diaphragm eventration, and puberty precox, a finding yet unreported in the literature. Conclusion: With this report, we aimed to expand the mutational spectrum and give insight into the importance of neurologic and skeletal system evaluation among other clinical features of FDH. Although gastrointestinal and genitourinary problems can occur during the course of the disease, to our knowledge, left-side diaphragm eventration and puberty precox are new features that have not been reported previously.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"11 5","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385271","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":"Novel Mutation in the HSD17B10 Gene Accompanied by Dysmorphic Findings in Female Patients","authors":"Kısmet Çıkı, Ceren Alavanda, Murat Kara","doi":"10.1159/000535589","DOIUrl":"https://doi.org/10.1159/000535589","url":null,"abstract":"Introduction: Hydroxysteroid 17-beta dehydrogenase type 10 (HSD10) protein is a mitochondrial enzyme. Multisystemic involvement occurs in HSD10 deficiency as in other mitochondrial diseases. HSD10 deficiency (disease) is rare. Less than 40 index cases have been reported so far. A female patient is even rarer because of X-linked transmission. Five index female cases have been reported. Case Presentation: We report a three-year-old female patient who was investigated due to microcephaly and global developmental delay. She had significant dysmorphic findings. The tiglylglycine peak was detected in urinary organic acid analysis. Other metabolic investigations and laboratory tests were unremarkable. Mild cerebral atrophy, mild ventricular dilation, thin corpus callosum, and an increase in T2 signal in the globus pallidus were revealed at brain magnetic resonance imaging. Heterozygous novel mutation in the HSD17B10 gene was found by whole-exome sequencing (WES) analysis. We started isoleucine-restricted diet and a “cocktail” of the mitochondrial vitamin. Discussion/Conclusion: We will see HSD10 disease patients more frequently with the increasing use of WES and genetic panels. Thus, different findings and phenotypes of the HSD10 disease will be revealed.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"51 13","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385774","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":"Whole-Exome Sequencing in Turkish Patients with Inherited Retinal Dystrophies Reveals Novel Variants in Ten Genes","authors":"Muserref Basdemirci, Hatice Kocak Eker","doi":"10.1159/000535590","DOIUrl":"https://doi.org/10.1159/000535590","url":null,"abstract":"<b><i>Introduction:</i></b> Inherited retinal dystrophies (IRDs) associated with more than 300 genes are a clinically and genetically heterogeneous group of retinal diseases. This study aimed to identify causative gene variants and molecular basis of Turkish patients with IRD. <b><i>Methods:</i></b> Whole-exome sequencing was performed in 28 unrelated patients. The potential pathogenicity of variants was evaluated using the American College of Medical Genetics variant interpretation guidelines, in silico prediction tools, published literature or Human Gene Mutation Database, and compatibility with inheritance patterns or known phenotypes. <b><i>Results:</i></b> Causative variants in 21 genes, including <i>MERTK</i>, <i>SNRP200</i>, <i>MYO7A</i>, <i>AIPL1</i>, <i>RDH12</i>, <i>OTX2</i>, <i>ADGRV1</i>, <i>RPGRIP1</i>, <i>SPATA7</i>, <i>USH2A</i>, <i>MFSD8</i>, <i>CDHR1</i>, <i>EYS</i>, <i>CACNA1F</i>, <i>CNGA3</i>, <i>RDH5</i>, <i>TULP1</i>, <i>BBS2</i>, <i>BEST1</i>, <i>RS1</i>, <i>GUCY2D</i> were detected in 26 (92.9%) of 28 patients. The most prevalent causative variants were observed <i>MERTK</i> (10.7% of cases), followed by <i>CDHR1</i>, <i>AIPL1</i>, <i>RDH12</i>, <i>SPATA7</i>, <i>CNGA3</i>, <i>TULP1</i> (7.1% of cases, each). The most common variant type in this study was missense variants (53%), followed by frameshift (21%), nonsense (20%), and splice (6%). Twelve novel variants, 6 of frameshift and 6 of missense, were detected in ten genes. Retinitis pigmentosa was the most common phenotype followed by Leber congenital amaurosis. <b><i>Conclusion:</i></b> This study provides an overview of causative gene variants in Turkish patients with IRD. Variants identified in this study expand the variant spectrum of IRD genes. We believe it is essential to combine molecular and clinical data to diagnose IRD patients, especially with the emergence of therapeutic options.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"24 16","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139148580","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":"Severe Early-Onset Obesity and Diabetic Ketoacidosis due to a Novel Homozygous c.169C>T p.Arg57* Variant in CEP19 Gene","authors":"A. Çayır, Ayberk Turkyilmaz, Hannah Rabenstein, Fadime Guven, Yuksel Sumeyra Karagoz, D. Vurallı, Martin Wabitsch, Huseyin Demirbilek","doi":"10.1159/000535253","DOIUrl":"https://doi.org/10.1159/000535253","url":null,"abstract":"Introduction: Early-onset severe obesity is usually the result of an underlying genetic disorder, and several genes have recently been shown to cause syndromic and nonsyndromic forms of obesity. The “centrosomal protein 19 (CEP19)” gene encodes for a centrosomal and ciliary protein. Homozygous variants in the CEP19 gene are extremely rare causes of early-onset severe monogenic obesity. Herein, we present a Turkish family with early-onset severe obesity with variable features. Methods: Sanger sequencing and whole-exome sequencing were performed to identify the genetic etiology in the family. Results: The index case was a 12-year-old female who presented with severe obesity (BMI of 62.7 kg/m2), metabolic syndrome, and diabetic ketoacidosis. Her nonidentical twin female siblings also had early-onset severe obesity, metabolic syndrome, and diabetes. In addition, one of the affected siblings had situs inversus abdominalis, polysplenia, lumbar vertebral fusion, and abnormal lateralization. A novel homozygous nonsense (c.169C>T, p. Arg57*) pathogenic variant was detected in exon 3 of the CEP19 gene in all affected members of the family. One unaffected sister and unaffected parents were heterozygous for the variant. This variant is predicted to cause a stop codon at amino acid sequence 57, leading to a truncated CEP19 protein. Discussion/Conclusion: Our study expands the phenotypical manifestations and variation database of CEP19 variants. The findings in one of our patients reaffirm its role in the assembly and function of both motile and immotile cilia.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"178 11","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139172473","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":"Delayed Bone Age in a Child with a Novel Loss-of-Function Variant in SETBP1 Gene Sheds Light on the Potential Role of SETBP1 Protein in Skeletal Development","authors":"G. Miolo, Davide Colavito, Lara Della Puppa, Giuseppe Corona","doi":"10.1159/000535057","DOIUrl":"https://doi.org/10.1159/000535057","url":null,"abstract":"Introduction: SETBP1 gene variants that decrease or eliminate protein activity have been associated with phenotypes characterized by speech apraxia and intellectual disabilities. This condition, distinctly separated from Schinzel-Giedion syndrome, is referred to as autosomal dominant mental retardation 29 (ADR29). Case Presentation: In this report, we present the case of a 6-year-old male patient exhibiting fine and global motor skill impairments along with expressive language delay. The patient carried a novel germline, heterozygous, de novo nonsense variant in the SETBP1 gene, specifically the c.532C>T variant, which prematurely terminates protein translation at amino acid 178, p.(Gln178*), and removes more than 10% of the reference protein isoform consisting of 1,596 amino acids. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, this variant has been classified as pathogenic. Conclusion: Given the limited number of ADR29 cases reported to date, it is critical to focus attention on the phenotypic features of each new individual and seek out previously undocumented defects. The clinical findings found in our patient align with current knowledge on the correlation between the genotypes characterized by loss-of-function variants in SETBP1 gene and a particular neurological phenotype. Furthermore, the presence of a severely delayed bone age in this patient, which we report for the first time, could indicate a possible indirect but significant contribution of the SETBP1 protein in bone development and maturation processes. This finding highlights the need for further investigation into the potential effects of SETBP1 gene variants on bone health and the possible involvement of the SETBP1 protein in skeletal growth and development.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"11 34","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138977046","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 Male Child with Infantile Epilepsy due to a Mosaic Missense Variant of PCDH19","authors":"Giulia Parmeggiani, R. Minardi, Antonella Boni, Jacopo Pruccoli, Antonella Pini, L. Licchetta, F. Bisulli, Claudio Graziano, Marco Seri","doi":"10.1159/000535144","DOIUrl":"https://doi.org/10.1159/000535144","url":null,"abstract":"Background: Pathogenic variants of PCDH19, located on the X-chromosome (Xq22.1), cause a rare epileptic encephalopathy with speech and development delay, seizures, behavioral and psychiatric problems. The specific underlying pathogenic mechanism is known as “cellular interference” that results in affected heterozygous females, normal hemizygous males and affected mosaic males but its functioning is not yet clear. Objectives: Reporting new cases of affected males is considered useful to a deeper insight. Subject and Method: We present the case of a three-year-old boy with early-onset seizures at 3 months of age, mild cognitive impairment, partial control of seizures with levetiracetam, normal brain imaging. Results: The patient has a mosaic pathogenic variant c.698A>G (p.Asp233Gly) in PCDH19 assessed by Next Generation Sequencing analysis. We have compared his characteristics with the genotypes and phenotypes of 34 PCDH19 mosaic males earlier reported in the literature. Finally, we have summarized today’s knowledge about phenotype-genotype correlation and pharmacological response in these patients. Conclusions: Our report confirms that the clinical picture of mosaic affected males, resembling that of females, can show a wide variability in severity of disease and underlines a stringent need to improve therapeutic approaches and to collect data on long-term follow-up.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"9 9","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138596871","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":"Report of a Novel Homozygous Intragenic DCC Duplication and a Review of Literature of Developmental Split-Brain Syndrome aka Horizontal Gaze Palsy with Progressive Scoliosis-2 with Impaired Intellectual Development Syndrome","authors":"Elisa Rahikkala, Taneli Väisänen, Liisa Ojala, Pia Pohjola, Minna Toivonen, R. Parkkola, Maria K. Haanpää","doi":"10.1159/000534772","DOIUrl":"https://doi.org/10.1159/000534772","url":null,"abstract":"Introduction: Horizontal gaze palsy with progressive scoliosis-2 (HGPPS2, MIM 617542) with impaired intellectual development aka developmental split-brain syndrome is an ultra-rare congenital disorder caused by pathogenic biallelic variants in the deleted in colorectal cancer (DCC) gene. Case Presentation: We report the clinical and genetic characterization of a Syrian patient with a HGPPS2 phenotype and review the previously published cases of HGPPS2. The genetic screening was performed using exome sequencing on Illumina platform. Genetic analysis revealed a novel DCC c.(?_1912)_(2359_?)dup, p.(Ser788Tyrfs*4) variant segregating recessively in the family. This type of variant has not been described previously in the HGPPS2 patients. To date, including the case reported here, three different homozygous pathogenic frameshift variants, one homozygous missense variant, and an intragenic duplication in the DCC gene have been reported in 8 patients with the HGPPS2 syndrome. Conclusion: The analysis of duplications and deletions in the DCC should be included in the routine genetic diagnostic evaluation of patients with suspected HGPPS2. This report expands the knowledge of phenotypic and genotypic spectrum of pathogenic variants causing HGPPS2.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 26","pages":""},"PeriodicalIF":1.1,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138601823","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}