Molecular Syndromology最新文献

{"title":"Co-Occurrence of Pallister-Killian Syndrome and Burkitt Lymphoma in a Patient with Near-Normal Neurocognitive Development.","authors":"Kosuke Izumi, Rebecca D Ganetzky, Gerald B W Wertheim, Cara M Skraban, Emma C Bedoukian, Alisha Wilkens, Christopher Fincher, Nina H Thomas, Jill P Ginsberg, Susan R Rheingold, Laura K Conlin, Matthew A Deardorff","doi":"10.1159/000530197","DOIUrl":"10.1159/000530197","url":null,"abstract":"<p><strong>Background: </strong>Pallister-Killian syndrome (PKS) is typically recognized by its features that include developmental delay, seizures, sparse temporal hair, and facial dysmorphisms. PKS is most frequently caused by mosaic supernumerary isochromosome 12p.</p><p><strong>Case presentation: </strong>Here, we report a patient with PKS who was subsequently diagnosed with Burkitt lymphoma. Following the successful treatment of lymphoma, this patient demonstrated very mild intellectual disability despite the diagnosis of PKS, which is usually associated with severe developmental delay.</p><p><strong>Discussion: </strong>This is the first reported patient with PKS and a hematologic malignancy. Although there is no significant reported association of tetrasomy 12p with cancer, the co-occurrence of two rare findings in this patient suggests a potential relationship. The localization of <i>AICDA</i>, a gene for which overexpression has been implicated in promoting t(8;14) noted in our patient's lymphoma, raises a potential mechanism of pathogenesis. In addition, this case indicates that children with PKS can demonstrate near-normal cognitive development.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 4","pages":"303-309"},"PeriodicalIF":1.1,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10020170","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 Missense Pathogenic Variant in a Conserved Region of <i>CNTNAP2</i> Is Associated with Obesity, Seizures, and Language Impairment in a Pakistani Family.","authors":"Sara Naudhani, Adeel Ahmad, Fariya Khan Bazai, Muhammad Tariq Pervez, Azqa Zafar, Sajjad Ali Shah, Nafeesa Raheem, Abdul Hameed Baloch, Muhammad Mushtaq, Shakeela Daud","doi":"10.1159/000529427","DOIUrl":"10.1159/000529427","url":null,"abstract":"<p><strong>Introduction: </strong>In a consanguineous family, seven siblings born in three sibships showed a syndromic disorder characterized by obesity, seizures, and language impairment phenotypes, which appeared at early age or developed during early childhood.</p><p><strong>Methods: </strong>By whole-exome sequencing and subsequent Sanger sequencing, a novel homozygous missense variant (c.3371 T>A [p.Ile1124Asn]) in exon 20 of the <i>CNTNAP2</i> gene was identified.</p><p><strong>Results: </strong>The pathogenic variant in this family is located within one of the laminin G-like 4 domains of CASPR2 and may cause loss of hydrophobic interactions of CASPR2 with its partner proteins. Single nucleotide and copy number variants in this gene have previously been related to Gilles de la Tourette syndrome, cortical dysplasia-focal epilepsy syndrome, schizophrenia, Pitt-Hopkins syndrome, and autism spectrum, attention deficit hyperactivity, and obsessive compulsive disorders. Yet, few studies described patients with <i>CNTNAP2</i> variants showing diet-induced obesity.</p><p><strong>Conclusion: </strong>This report expands the phenotypic spectrum of this rare syndrome and provides deeper insights by documenting the clinical features and genetic findings of the patients.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 4","pages":"293-302"},"PeriodicalIF":1.1,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155239","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":"DPAGT1-CDG: Report of Two New Pediatric Patients and Brief Review of the Literature.","authors":"Özlem Özsoy, Tayfun Cinleti, Çağatay Günay, Gamze Sarıkaya Uzan, Mehmet Can Yeşilmen, Hanns Lochmüller, Rita Horvath, Uluç Yiş, Yavuz Oktay, Semra Hiz Kurul","doi":"10.1159/000529494","DOIUrl":"10.1159/000529494","url":null,"abstract":"<p><strong>Introduction: </strong>Congenital glycosylation disorders are multisystem diseases with heterogeneous clinical manifestations caused by defects in the synthesis of the glycan moiety of glycoproteins or glycolipids or the binding of glycans to proteins and lipids. DPAGT1 (UDP-GlcNAc: dolichol phosphate N-acetylglucosamine-1-phosphotransferase) is an initiating protein in the biosynthetic pathway of dolichol-linked oligosaccharides required for protein N-glycosylation. Pathogenic variants in <i>DPAGT1</i> (UDP-GlcNAc: dolichol phosphate N-acetylglucosamine-1-phosphotransferase) gene cause a rare type of congenital glycosylation disorder called DPAGT1-CDG (formerly CDG-Ij) (OMIM #608093). It is a rare autosomal recessive disease or a milder version with congenital myasthenic syndrome known as DPAGT1-CMS. A severe disease course with hypotonia, cataracts, skeletal deformities, resistant epilepsy, intellectual disability, global developmental delay, premature death has been described in most patients with DPAGT1-CDG.</p><p><strong>Patient presentation: </strong>We describe two patients with variants in the <i>DPAGT1</i> gene: an 8-month-old boy with a homozygous, missense <i>DPAGT1</i>:c.339T>G (p.Phe113Leu) novel variant and a 13-year-old female patient with compound heterozygous variants, <i>DPAGT1</i>:c.466C>T (p.Arg156Cys, R156C) and <i>DPAGT1</i>:c.161+5G>A. While the 8-month-old patient was diagnosed with congenital cataract at the age of 1 month, had dysmorphic findings, and epilepsy, clinical symptoms in the other patient appeared later but with more prominent muscle weakness, behavioral disorder, dysmorphic findings, and no epilepsy.</p><p><strong>Discussion: </strong>Cholinesterase inhibitor therapy was found to be effective in patients against muscle weakness, supporting <i>DPAGT1</i> deficiency as the underlying etiology. We started pyridostigmine treatment in our patient with more pronounced muscle weakness, and we saw its benefit. We aimed to present our patients diagnosed with DPAGT1-CDG due to different variants in the same gene and different clinical presentations, treatment and to compare them with other patients in the literature.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 4","pages":"322-330"},"PeriodicalIF":1.1,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155951","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":"X-Linked Hydrocephalus with New <i>L1CAM</i> Pathogenic Variants: Review of the Most Prevalent Molecular and Phenotypic Features.","authors":"Rania R Ahmed, Amina M Medhat, Germine M Hamdy, Laila K E Effat, Mohamed S Abdel-Hamid, Ghada M H Abdel-Salam","doi":"10.1159/000529545","DOIUrl":"10.1159/000529545","url":null,"abstract":"<p><strong>Introduction: </strong>The underlying molecular defects of congenital hydrocephalus are heterogeneous and many isolated forms of hydrocephalus remain unsolved at the molecular level. Congenital hydrocephalus in males associated with agenesis of the corpus callosum is a notable characteristic of <i>L1CAM</i> gene which is by far the most common genetic etiology of congenital hydrocephalus.</p><p><strong>Methods and results: </strong>Sequencing of the <i>L1CAM</i> gene on 25 male patients/fetuses who had been presented with hydrocephalus revealed 6 patients and two fetuses with different hemizygous pathogenic variants. Our study identified 4 novel variants and 4 previously reported. The detection rate was 32%, and all the variants were shown to be maternally inherited. Nonsense variants were detected in 3 patients, while missense variants were detected in 2 patients. Frameshift, silent, and splicing variant, each was detected in 1 patient. The clinical manifestations of the patients are in line with those frequently observed including communicating hydrocephalus and agenesis of the corpus callosum. Moreover, rippled ventricles with subdural collection and asymmetry of ventricles after shunt operation were seen in 1 patient and 2 patients, respectively. In addition, abnormal basal ganglia were found in 4 patients which seems to be an additional distinct new finding. We also describe a patient with novel nonsense variant with the rare association of Hirschsprung's disease. This patient displayed additionally multiple porencephalic cysts and encephalomalacia secondary to hemorrhage due to repeated infections after shunt operation. The patients with the missense variants showed long survival, while those with truncating variants showed poor prognosis.</p><p><strong>Conclusion: </strong>This report adds knowledge of novel pathogenic variants to the <i>L1CAM</i> variant database. Furthermore, we evaluated the clinical and imaging data of these patients.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 4","pages":"283-292"},"PeriodicalIF":1.1,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41148918","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":"Identification of a Novel de novo Splicing Mutation in Duchenne Muscular Dystrophy Gene in an Iranian Family.","authors":"Saeideh Kavousi, Azam Pourahmadiyan, Fatemeh Soleymani, Mehrdad Noruzinia","doi":"10.1159/000528035","DOIUrl":"10.1159/000528035","url":null,"abstract":"<p><strong>Introduction: </strong>Duchenne muscular dystrophy (DMD) (NM_004006.3) is one of the most notable neuromuscular disorders of early years. The majority of DMD cases are caused by deletions or duplications in dystrophin, while point mutations are less prevalent in dystrophin abnormalities. It is a common knowledge that the severity of the disease depends on the effect of the mutation on the translational reading frame of the dystrophin mRNA.</p><p><strong>Case report: </strong>We studied an 8-year-old boy with relevant clinical presentations for DMD. Deletion/duplication screening was performed by using multiplex ligation-dependent probe amplification, and whole-exome sequencing was conducted in order to identify potential variants. A novel de novo splice site variant was identified in the <i>DMD</i> gene (DMD: c.8548-2A>G). To explore the effect of a novel variant in <i>DMD</i>, various in silico analyses were carried out to investigate the pathogenicity of the causative variant. To study the structure of a DMD protein and information on how the genetic variant impacts splicing site in models of wild-type and mutated DMD, we carried out different computational studies. Sanger sequencing was performed for the purpose of variant confirmation and familial segregation analysis.</p><p><strong>Discussion: </strong>This novel de novo variant was predicted to have an effect on splicing, which leads to DMD due to its significant impacts on dystrophin functionality. The novel mutation would be expected to disrupt the protein structure.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 4","pages":"331-340"},"PeriodicalIF":1.1,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41178840","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":"Shifting the Focus of <i>Molecular Syndromology</i> from Individual Diagnoses to Outcome Analyses.","authors":"","doi":"10.1159/000531738","DOIUrl":"10.1159/000531738","url":null,"abstract":"","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 4","pages":"267-269"},"PeriodicalIF":0.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10360572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9861998","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":"Diagnostic Gene Panel Testing in (Non)-Syndromic Patients with Cleft Lip, Alveolus and/or Palate in the Netherlands.","authors":"Lisca Florence Wurfbain, Inge Lucia Cox, Maria Francisca van Dooren, Augusta Maria Antonia Lachmeijer, Virginie Johanna Maria Verhoeven, Johanna Maria van Hagen, Malou Heijligers, Jolien Sietske Klein Wassink-Ruiter, Saskia Koene, Saskia Mariska Maas, Hermine Elisabeth Veenstra-Knol, Johannes Kristian Ploos van Amstel, Maarten Pieter Gerrit Massink, Aebele Barber Mink van der Molen, Marie-José Henriette van den Boogaard","doi":"10.1159/000530256","DOIUrl":"10.1159/000530256","url":null,"abstract":"<p><strong>Objectives: </strong>Clefts of the lip, alveolus and/or palate (CLA/P) are the most common craniofacial congenital malformations in humans. These oral clefts can be divided into non-syndromic (isolated) and syndromic forms. Many cleft-related syndromes are clinically variable and genetically heterogeneous, making it challenging to distinguish syndromic from non-syndromic cases. Recognition of syndromic/genetic causes is important for personalized tailored care, identification of (unrecognized) comorbidities, and accurate genetic counseling. Therefore, next generation sequencing (NGS)-based targeted gene panel testing is increasingly implemented in diagnostics of CLA/P patients. In this retrospective study, we assess the yield of NGS gene panel testing in a cohort of CLA/P cases.</p><p><strong>Methods: </strong>Whole exome sequencing (WES) followed by variant detection and interpretation in an a priori selected set of genes associated with CLA/P phenotypes was performed in 212 unrelated CLA/P patients after genetic counseling between 2015 and 2020. Medical records including family history and results of additional genetic tests were evaluated.</p><p><strong>Results: </strong>In 24 CLA/P cases (11.3%), a pathogenic genetic variant was identified. Twenty out of these 24 had a genetic syndrome requiring specific monitoring and follow-up. Six of these 24 cases (25%) were presumed to be isolated CLA/P cases prior to testing, corresponding to 2.8% of the total cohort. In eight CLA/P cases (3.8%) without a diagnosis after NGS-based gene panel testing, a molecular diagnosis was established by additional genetic analyses (e.g., SNP array, single gene testing, trio WES).</p><p><strong>Conclusion: </strong>This study illustrates NGS-based gene panel testing is a powerful diagnostic tool in the diagnostic workup of CLA/P patients. Also, in apparently isolated cases and non-familial cases, a genetic diagnosis can be identified. Early diagnosis facilitates personalized care for patients and accurate genetic counseling of their families.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 4","pages":"270-282"},"PeriodicalIF":1.1,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10395635","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":"Recurrent Mutation (p.Arg718Pro) in the <i>COMP</i> Gene with Clinical Heterogeneity of Pseudoachondroplasia.","authors":"Jaime Toral López, Luz María González Huerta","doi":"10.1159/000528980","DOIUrl":"10.1159/000528980","url":null,"abstract":"<p><strong>Introduction: </strong>Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are allelic and caused by mutations in the <i>COMP</i> gene. Other mutations in the genes <i>MMP13</i>, <i>AIFM1</i>, <i>B3GALT6</i>, <i>MATN3</i>, <i>COL9A1</i>, <i>COL9A2</i>, <i>COL9A3</i>, and <i>SLC26A2</i> have also been associated with evidence of dysplasia in the epiphysis, metaphysis, and spine.</p><p><strong>Case presentation: </strong>We report on the first Mexican patient diagnosed with PSACH. The diagnosis was confirmed by identifying a recurrent heterozygous mutation c.2153G>C (p.Arg718Pro) in the <i>COMP</i> gene using whole-exome sequencing.</p><p><strong>Discussion: </strong>The anterior spindle-shaped vertebral bodies and severe short stature are not observed in patients carrying p.Arg718Pro, identifying another amino acid site associated with clinical heterogeneity. Reporting new cases with clinical heterogeneity in terms of phenotype plays a crucial role in understanding PSACH and MED pathogenesis. The most important aspect of this presentation is providing a new perspective on a recognized clinical scenario, thus setting the standard for better genetic counseling.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 4","pages":"341-346"},"PeriodicalIF":1.1,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41116024","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":"Pure Interstitial Trisomy 11q Arising from a Nonrecurrent 11q13.1q22.3 Mosaic Intrachromosomal Duplication in a Patient with Craniofacial Dysmorphism and Genital Anomalies.","authors":"Daniel Martínez Anaya, María Del Rocío Juárez-Velázquez, Sinuhé Reyes Ruvalcaba, María Del Pilar Navarrete-Meneses, Consuelo Salas Labadía, Esther Lieberman Hernández, Patricia Pérez-Vera","doi":"10.1159/000528472","DOIUrl":"10.1159/000528472","url":null,"abstract":"<p><strong>Introduction: </strong>The pure interstitial trisomy 11q11q23.2 is an uncommon genomic disorder associated with nonrecurrent intrachromosomal duplications. The phenotype is characterized by intellectual disability and craniofacial abnormalities. Given their uncommonness, a comprehensive genotype-phenotype correlation has not fully been defined.</p><p><strong>Case presentation: </strong>We report the clinical and cytogenomic characterization of a 5-year-old boy with intellectual disability, psychomotor retardation, craniofacial dysmorphism, genital anomalies, and pure interstitial trisomy 11q arising from a nonrecurrent 11q13.1q22.3 intrachromosomal duplication in a high-mosaic state (>80%). The duplicated chromosome was characterized by cytogenetics, multicolor banding FISH, and SNP array. We demonstrated the wide mosaic distribution of the 11q duplication by interphase FISH in tissues from different embryonic germ layers. The duplication involves a copy number gain of 45.3 Mb containing 22 dosage-sensitive genes. We confirmed the overexpression of dosage-sensitive genes along the duplicated region using RT-qPCR.</p><p><strong>Discussion: </strong>Only 8 patients have been described. Our patient shares clinical features with previous reports but differs from them by the presence of genital anomalies. We provide a detailed clinical review and an accurate genotype-phenotype correlation and propose <i>PC</i>, <i>NDUFV1</i>, <i>FGF3</i>, <i>FGF4</i>, and <i>DHCR7</i> as dosage-sensitive genes with a possible role in the clinical spectrum of our patient; however, expression changes of <i>FGF3/4</i> were not detected since they must be regulated in a spatiotemporal way. This patient contributes to the accurate description of the pure interstitial trisomy 11q. Future reports could continue to delineate the description, considering the relationship between the chromosome segment and the genes involved.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 4","pages":"310-321"},"PeriodicalIF":1.1,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41133931","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":"Expanding the p.(Arg85Trp) Variant-Specific Phenotype of HNF4A: Features of Glycogen Storage Disease, Liver Cirrhosis, Impaired Mitochondrial Function, and Glomerular Changes.","authors":"Mara Grassi, Bernard Laubscher, Amit V Pandey, Sibylle Tschumi, Franziska Graber, André Schaller, Marco Janner, Daniel Aeberli, Ekkehard Hewer, Jean-Marc Nuoffer, Matthias Gautschi","doi":"10.1159/000529306","DOIUrl":"10.1159/000529306","url":null,"abstract":"<p><strong>Introduction: </strong>The p.(Arg85Trp) variant-specific phenotype of hepatocyte nuclear factor 4 alpha shows a complex clinical picture affecting three different organ systems and their corresponding metabolisms. Little is known about the molecular mechanisms involved and their relationship with the diverse symptoms seen in the context of this specific variant. Here, we present data of a new patient that expand the clinical phenotype, suggesting possible disease mechanisms.</p><p><strong>Case presentation: </strong>Clinical data were extracted from the patient's charts. The liver, kidney, and muscle were analyzed with routine histology and electron microscopy. Mitochondrial function was assessed by respirometric analyses and enzymatic activity assays. Structure and sequence analyses of this specific variant were investigated by in silico analyses. Our patient showed the known features of the variant-specific phenotype, including macrosomia, congenital hyperinsulinism, transient hepatomegaly, and renal Fanconi syndrome. In addition to that, she showed liver cirrhosis, chronic kidney failure, and altered mitochondrial morphology and function. The clinical and biochemical phenotype had features of a new type of glycogen storage disease.</p><p><strong>Discussion: </strong>This case expands the p.(Arg85Trp) variant-specific phenotype. Possible pathomechanistic explanations for the documented multiorgan involvement and changes of symptoms and signs during development of this ultra-rare but instructive disorder are discussed.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 4","pages":"347-361"},"PeriodicalIF":1.1,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41148917","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}