Molecular Syndromology最新文献_第7页

D-Bifunctional Protein Deficiency Type III: Two Turkish Cases and a Novel HSD17B4 Gene Variant. d -双功能蛋白缺乏症III型：两个土耳其病例和一个新的HSD17B4基因变体

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-03-28 DOI: 10.1159/000545474

Ayşenur Engin Erdal, Berrak Bilginer Gürbüz, Aynur Küçükçongar Yavaş, Çiğdem Seher Kasapkara

{"title":"D-Bifunctional Protein Deficiency Type III: Two Turkish Cases and a Novel HSD17B4 Gene Variant.","authors":"Ayşenur Engin Erdal, Berrak Bilginer Gürbüz, Aynur Küçükçongar Yavaş, Çiğdem Seher Kasapkara","doi":"10.1159/000545474","DOIUrl":"10.1159/000545474","url":null,"abstract":"Introduction: Bi-allelic variants in the 17-hydroxysteroid dehydrogenase type 4 gene (HSD17B4) cause the extremely rare autosomal recessive disorder known as peroxisomal D-bifunctional protein deficiency (D-BPD) (#OMIM 261515). This protein mediates hydration and dehydrogenation in the peroxisomal fatty acid β-oxidation pathway. Because of this, very long-chain fatty acids (VLCFAs), branched fatty acids (pristanic acid), and bile acid components cannot be broken down without it. Clinically, it causes developmental delay with neonatal hypotonia, seizures, and dysmorphic features. The D-BPD is divided into four subtypes according to the region affected by the variant causing the disorder.Case presentation: Two newborns presented with severe hypotonia, intractable seizures, and dysmorphic facial features (microretrognathia, hypertelorism). These cases showed high levels of VLCFAs and were diagnosed by next-generation gene sequencing tests. We found a known homozygous variant (c.46G>A/p.Gly16Ser) in the HSD17B4 gene of case 1, which had been linked to D-BPD type III before. Case 1 developed adrenal insufficiency during follow-up. In case 2, we discovered a novel homozygous variant (c. 559A>T, p. Ile187Phe) in the HSD17B4 gene in exon 8 that led to the development of D-BPD type III. The American College of Medical Genetics and Genomics (ACMG) classifies this missense variant as likely pathogenic.Discussion: The D-BPD type III cases profiled in this report exhibit a severe phenotype, which includes dysmorphic facial features, severe hypotonia, and refractory seizures that manifest from birth. One month after the VLCFAs analysis revealed something suggestive of a peroxisomal disorder, a targeted gene panel analysis could confirm the diagnosis.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"1-8"},"PeriodicalIF":0.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144097","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}

引用次数: 0

A Novel Homozygous Missense SCUBE3 Variant with Protein Modeling in a Patient Diagnosed as Short Stature, Facial Dysmorphism, and Skeletal Anomalies with or without Cardiac Anomalies 2. 一种新的纯合错义SCUBE3变异与蛋白质建模的患者诊断为身材矮小，面部畸形，骨骼异常伴或不伴心脏异常2。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-03-28 DOI: 10.1159/000545570

Burcu Yeter, Batın Ilgıt Sezgin, Yunus Emre Dilek, Yasemin Kendir Demirkol, Arzu Selamioğlu, Heves Kırmızıbekmez, Hande Kaymakçalan Çelebiler, Günseli Bayram Akçapınar

{"title":"A Novel Homozygous Missense SCUBE3 Variant with Protein Modeling in a Patient Diagnosed as Short Stature, Facial Dysmorphism, and Skeletal Anomalies with or without Cardiac Anomalies 2.","authors":"Burcu Yeter, Batın Ilgıt Sezgin, Yunus Emre Dilek, Yasemin Kendir Demirkol, Arzu Selamioğlu, Heves Kırmızıbekmez, Hande Kaymakçalan Çelebiler, Günseli Bayram Akçapınar","doi":"10.1159/000545570","DOIUrl":"https://doi.org/10.1159/000545570","url":null,"abstract":"Introduction: Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2 is a very rare genetic disorder caused by biallelic pathogenic variants in the SCUBE3 gene and has been reported in approximately 20 patients to date. SCUBE3 protein exhibits significant expression in various tissues, including primary osteoblasts, long bones, and the cartilage of the axial skeleton throughout development, while also playing a regulatory role in the FGF, Hedgehog, and TGF-β signaling pathways.Case presentation: We report a 13-year-old female patient from a consanguineous Turkish family with a novel homozygous missense variant, c.908G>C (p.Cys303Ser) in the SCUBE3 gene identified, through exome sequencing. The patient exhibited prenatal growth retardation, short stature, microcephaly, distinctive facial traits, such as long face, high arched eyebrows, epicanthus, blepharoptosis, hypotelorism, high nasal bridge, micrognathia, and large ears, dental anomalies, and skeletal abnormalities, including scoliosis, eleven pairs of ribs, mild radial bowing, irregular endplates in the lower thoracic vertabrae, and narrow iliac wings.Conclusion: Protein modeling using AlphaFold3 revealed disruption of a critical disulfide bridge within the seventh epidermal growth factor-like repeat, likely affecting protein stability. In this study, we aimed to further characterize the clinical, radiological, and molecular features of this disorder with protein modeling.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"1-9"},"PeriodicalIF":0.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062790","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}

引用次数: 0

Clinical and Genetic Aspects of Verheij Syndrome in Two Cases. 两例Verheij综合征的临床与遗传学分析。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-03-25 DOI: 10.1159/000545448

Yade Dilay Kursat, Hazal Sezginer Guler, Drenushe Zhuri, Hakan Gurkan, Sinem Yalcintepe

引用次数: 0

A Novel de novo Exceptional Complex Chromosomal Rearrangement Involving 5 Chromosomes Resulting in Neurodevelopmental Delay and Dysmorphism. 一种涉及5条染色体的新的异常复杂染色体重排导致神经发育迟缓和畸形。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-03-25 DOI: 10.1159/000545465

Sabri Aynacı, Sinem Kocagil, Coşkun Yarar, Efsun Tosumoğlu, Ebru Erzurumluoğlu Gökalp, Mehmet Burak Mutlu, Sevilhan Artan

{"title":"A Novel de novo Exceptional Complex Chromosomal Rearrangement Involving 5 Chromosomes Resulting in Neurodevelopmental Delay and Dysmorphism.","authors":"Sabri Aynacı, Sinem Kocagil, Coşkun Yarar, Efsun Tosumoğlu, Ebru Erzurumluoğlu Gökalp, Mehmet Burak Mutlu, Sevilhan Artan","doi":"10.1159/000545465","DOIUrl":"https://doi.org/10.1159/000545465","url":null,"abstract":"Introduction: Complex chromosomal rearrangements (CCRs) are constitutive structural aberrations involving three or more chromosomal breaks on three or more chromosomes resulting from complex events such as fork stalling and template switching, microhomology-mediated break-induced repair, or breakage-fusion-bridge cycles.Case presentation: Here we report an 11-year-old female that was referred to our outpatient clinics for learning disability and dysmorphic features. Due to clinical findings, karyotype analysis was done initially, and a CCR involving five chromosomes was detected. Fluorescence in situ hybridization (FISH) analysis and chromosomal microarray analysis were done subsequently. Balanced translocations were observed between chromosomes 1, 5, 7, and 10, a balanced paracentric inversion of chromosome 2, and two interstitial deletions in the long arm of the chromosome 5. Optical genome mapping was done to further investigate this exceptional CCR and a paracentric inversion that was associated with the two interstitial deletions was detected in the long arm of chromosome 5.Conclusion: Molecular cytogenetic techniques, such as microarray and FISH, are essential for detecting copy number variations at CCRs that appear to be balanced by karyotyping. Nonetheless, optical genome mapping enhances the resolution offering a valuable complement to traditional cytogenetic techniques.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"1-9"},"PeriodicalIF":0.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057481","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}

引用次数: 0

A Novel PTCH1 Non-Canonical Splice Region Variant Associated with Gorlin Syndrome: A Case Report. 与Gorlin综合征相关的一种新的PTCH1非典型剪接区变异：一例报告。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-03-24 DOI: 10.1159/000545453

Miriam J Smith, Emily-Jayne Shell, George J Burghel, Megan Carney, Sarah J Waller, Alan Hakim, D Gareth Evans

引用次数: 0

Clinical Characterization and Cytogenetic-Molecular Study of a Patient with a Ring Chromosome 12. 12号染色体环状患者的临床特征和细胞遗传学分子研究。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-03-20 DOI: 10.1159/000545023

Vinícius Almeida da Nóbrega, Gabriella Rodrigues Dos Santos, Maria Isabel Melaragno, Rayana Elias Maia

{"title":"Clinical Characterization and Cytogenetic-Molecular Study of a Patient with a Ring Chromosome 12.","authors":"Vinícius Almeida da Nóbrega, Gabriella Rodrigues Dos Santos, Maria Isabel Melaragno, Rayana Elias Maia","doi":"10.1159/000545023","DOIUrl":"https://doi.org/10.1159/000545023","url":null,"abstract":"Introduction: Ring chromosomes generally result from the fusion of breaks at the ends of both arms of a chromosome, typically leading to the loss of genetic material from these ends.Case presentation: We report the case of a four-year-old patient who exhibits multiple café-au-lait spots, hypochromic spots, bitemporal narrowing, bilateral epicanthus, patent foramen ovale, and multiple brain abnormalities identified through magnetic resonance imaging. Karyotyping revealed a ring chromosome: r(12). Chromosomal microarray analysis revealed a ∼3.6 Mb deletion in the short arm and a ∼1.2 Mb deletion in the long arm of chromosome 12. The patient's phenotype is consistent with these genetic imbalances. To investigate ring chromosome instability and mosaicism, 200 metaphases were analyzed using G-banding and FISH with a whole chromosome painting probe, identifying 166 cells with a 46,XX,r(12) karyotype, 20 cells with monosomy 12, eight with a dicentric ring chromosome, three with two monocentric rings, two with two interlocked dicentrics, and one with an open ring chromosome.Conclusion: This study provided a detailed characterization of the ring rearrangement of chromosome 12, the first with SNP array, enhancing the understanding of its genetic and phenotypic implications and contributing to expanding knowledge about this condition. Additionally, the findings can aid in better understanding the patient's prognosis, clinical follow-up, and genetic counseling.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"1-7"},"PeriodicalIF":0.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021460","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}

引用次数: 0

Expanding the Genetic Landscape of RASopathies: Significance of Including NF1 in Targeted Panels. 扩大RASopathies的遗传景观：将NF1纳入目标小组的意义。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-03-18 DOI: 10.1159/000545192

Yasemin Kendir-Demirkol, Burcu Yeter, Metin Eser, Murat Hakki Yarar

{"title":"Expanding the Genetic Landscape of RASopathies: Significance of Including NF1 in Targeted Panels.","authors":"Yasemin Kendir-Demirkol, Burcu Yeter, Metin Eser, Murat Hakki Yarar","doi":"10.1159/000545192","DOIUrl":"10.1159/000545192","url":null,"abstract":"Introduction: RASopathies are genetic disorders linked to the RAS/MAPK signaling pathway, including Noonan syndrome and related conditions. These disorders have overlapping features and variable phenotypes, making diagnosis challenging. This study examines the clinical and genetic characteristics of RASopathies in pediatric patients to improve diagnostic accuracy and identify novel pathogenic variants.Methods: A total of 23 patients, who were not related to each other and were clinically diagnosed with RASopathy, participated in the study. Patients underwent next-generation sequencing (NGS) panel analyses of 14 RASopathy genes.Results: Pathogenic variants were found in 18 out of 23 patients (78%). The most common variants were in PTPN11 and SOS1. Novel variants were identified in KRAS and NF1 expanding the known genetic spectrum. Frequent clinical features included distinctive facial features, growth delays, and heart defects, notably pulmonary stenosis. Intellectual disability was more common in patients with PTPN11 variants, while SOS1 variants were associated with unique features such as previously unreported polydactyly and choanal atresia.Conclusion: Targeted NGS panels improve diagnosis of RASopathies, with a variant detection rate of 78%. Including the NF1 gene, even without signs of neurofibromatosis, enhances diagnostic success. This study adds to our understanding of genotype-phenotype relationships in RASopathies and highlights new clinical features tied to SOS1 variants. Comprehensive genetic testing supports earlier and more personalized care for patients with RASopathies.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281477","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}

引用次数: 0

A Novel PNPLA2 Variant in a Female Patient with Neutral Lipid Storage Disease with Myopathy and Hypogonadotropic Hypogonadism. 中性脂质储存病合并肌病和促性腺功能减退症女性患者中一种新的PNPLA2变异

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-02-01 Epub Date: 2024-10-03 DOI: 10.1159/000541285

Hüseyin Bahadır Şenol, Pelin Teke Kısa, Bahar Kulu, Hale Ören, Nur Arslan, Uluç Yiş

{"title":"A Novel PNPLA2 Variant in a Female Patient with Neutral Lipid Storage Disease with Myopathy and Hypogonadotropic Hypogonadism.","authors":"Hüseyin Bahadır Şenol, Pelin Teke Kısa, Bahar Kulu, Hale Ören, Nur Arslan, Uluç Yiş","doi":"10.1159/000541285","DOIUrl":"10.1159/000541285","url":null,"abstract":"Background: Neutral lipid storage disease with myopathy (NLSDM) is a rare autosomal recessive disorder characterized by aberrant triacylglycerol metabolism due to mutations in the patatin-like phospholipase domain-containing 2 (PNPLA2) gene.Case presentation: This report presents a case study of a 14-year-old female patient exhibiting symptoms of NLSDM, including recurrent abdominal pain, fatigue, leg pain, and hepatosteatosis. Diagnostic investigations revealed elevated creatinine kinase levels, myopathic findings on electromyography, magnetic resonance imaging findings showing gluteal involvement and Jordans' bodies on peripheral smear. Clinical exome panel showed homozygous of PNPLA2 c.496G>C p.Asp166His (NM_020376.4) variant. The clinical manifestations, diagnostic challenges, and implications of this novel variant are discussed in the context of current literature. Hypogonadotropic hypogonadism was confirmed in this patient after eliminating possible underlying causes. This was a novel manifestation, and hormone replacement therapy was planned.Conclusion: This case underscores the significance of genetic testing in elucidating the molecular basis of NLSDM and emphasizes the necessity of comprehensive clinical evaluation for accurate diagnosis and management.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"16 1","pages":"93-98"},"PeriodicalIF":0.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256168","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}

引用次数: 0

Kabuki Syndrome and Charcot-Marie-Tooth Disease Co-Occurrence: Unique Case with Novel Variant. 歌舞伎综合征与腓骨肌赘病共现：独特病例与新变异。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-02-01 Epub Date: 2024-07-29 DOI: 10.1159/000540207

Ahmet Kablan, Esma Erturkmen Aru

{"title":"Kabuki Syndrome and Charcot-Marie-Tooth Disease Co-Occurrence: Unique Case with Novel Variant.","authors":"Ahmet Kablan, Esma Erturkmen Aru","doi":"10.1159/000540207","DOIUrl":"10.1159/000540207","url":null,"abstract":"Introduction: Kabuki syndrome (KS) is a rare syndrome, characterized by dysmorphic features, congenital abnormalities, and developmental problems. The primary genetic causes are variants in the KMT2D and KDM6A genes. There are few KS patients with KDM6A variants, especially in Turkey. Charcot-Marie-Tooth (CMT) disease, with various subtypes, is the most common inherited peripheral neuropathy.Case presentation: We present a case of a 7-year-old girl with characteristic dysmorphic features, neonatal hypotonia, developmental delay, and short stature. Exome sequencing revealed a novel heterozygous variant in KDM6A, along with a concurrent suspected diagnosis of CMT disease with CNV analysis, not previously reported in the literature. PMP22 duplication was later confirmed in the patient and symptomatic mother with MLPA test.Conclusion: We report a unique case of dual diagnosis with a novel de novo heterozygous variant in KDM6A and PMP22 duplication in the same patient, highlighting the additive use of exome sequencing for CNVs and, moreover, unraveling the complexity of rare diseases, particularly when multiple conditions coexist.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"16 1","pages":"55-60"},"PeriodicalIF":0.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256860","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}

引用次数: 0

PACS2, PACS1, and VACTERL: A Clinical Overlap. PACS2， PACS1和VACTERL：临床重叠。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-02-01 Epub Date: 2024-08-07 DOI: 10.1159/000539473

Hannah Massey, Stephen Tennant, John Dean

{"title":"PACS2, PACS1, and VACTERL: A Clinical Overlap.","authors":"Hannah Massey, Stephen Tennant, John Dean","doi":"10.1159/000539473","DOIUrl":"10.1159/000539473","url":null,"abstract":"Introduction: Whole-exome sequencing has led to the discovery of new genes involved in developmental delay. Two of these are the evolutionary linked proteins phosphofurin acidic cluster sorting protein 1 (PACS1) and phosphofurin acidic cluster sorting protein 2 (PACS2), which function as metabolic switches. We present a case of a patient with the previously described PACS2 c.624G>A; p.Glu209Lys variant, with distinct clinical features, suggesting an overlap between the two conditions.Case presentation: The patient presented with infantile epilepsy, developmental delay, and cerebellar hypoplasia previously described with PACS2. However, he also had novel features not noted in the literature before; this included anal atresia, tetralogy of Fallot, and vertebral abnormalities. This constellation of features had given him a label of VACTERL.Conclusion: Cardiac abnormalities are more commonly seen in PACS1 variants, and this case strengthens the phenotypic similarities between the two conditions. We also explore the genetic mechanisms causing the cardiac and anal anomalies seen in our patient and suggest the PACS2 disease spectrum should be expanded.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"16 1","pages":"29-32"},"PeriodicalIF":0.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256954","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}

引用次数: 0