Molecular Syndromology最新文献_第3页

Confirmation of the Hotspot Variant in MAP3K20 Responsible for Deafness, Ectodermal Dysplasia, Craniosynostosis, Ectrodactyly, and Skeletal Anomaly Spectrum. MAP3K20中导致耳聋、外胚层发育不良、颅缝闭合、电指畸形和骨骼异常谱的热点变异的确认。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-07-17 DOI: 10.1159/000547411

Elifcan Taşdelen, Müzeyyen Gönül, Bahar Öztelcan Gündüz, Çiğdem Üner, Afife Büke, Abdullah Sezer

{"title":"Confirmation of the Hotspot Variant in MAP3K20 Responsible for Deafness, Ectodermal Dysplasia, Craniosynostosis, Ectrodactyly, and Skeletal Anomaly Spectrum.","authors":"Elifcan Taşdelen, Müzeyyen Gönül, Bahar Öztelcan Gündüz, Çiğdem Üner, Afife Büke, Abdullah Sezer","doi":"10.1159/000547411","DOIUrl":"https://doi.org/10.1159/000547411","url":null,"abstract":"Introduction: Heterozygous variants in MAP3K20 have been implicated in a recently identified syndromic form of ectodermal dysplasia, distinguished by a unique combination of ectrodactyly, craniosynostosis, bilateral sensorineural hearing loss, and skeletal anomalies such as transverse limb defect, and brachydactyly.Case presentation: We present an 11-year-old male with ectrodactyly, ectodermal dysplasia, bilateral sensorineural hearing loss, and cutaneous syndactyly in both hands. A de novo heterozygous variant, c.837_839del p.(Asn279del), in MAP3K20 was identified in his whole exome sequencing.Conclusion: The results of this study emphasize the critical role of MAP3K20 as a key gene in conditions involving ectrodactyly, craniosynostosis, bilateral sensorineural hearing loss, ectodermal features, transverse limb defect, and brachydactyly. We highlight the importance of prioritizing the recurrent p.(Asn279del) variant in genetic testing for affected individuals. Furthermore, we propose an acronym for this dominant disorder caused by the MAP3K20 gene variants: DECES (Dominant/Deafness, Ectodermal Dysplasia, Craniosynostosis, Ectrodactyly, Skeletal anomalies).","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253319","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

Genetic Analysis Strategy for Diagnosing Congenital Heart Disease. 先天性心脏病诊断的遗传分析策略。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-07-14 DOI: 10.1159/000547412

Natasha Malgarezi de Moraes, Bruna Lixinski Diniz, Ana Kalise Böttcher, Marcela Rodrigues Nunes, Rafaella Mergener, Paulo Ricardo Gazzola Zen

{"title":"Genetic Analysis Strategy for Diagnosing Congenital Heart Disease.","authors":"Natasha Malgarezi de Moraes, Bruna Lixinski Diniz, Ana Kalise Böttcher, Marcela Rodrigues Nunes, Rafaella Mergener, Paulo Ricardo Gazzola Zen","doi":"10.1159/000547412","DOIUrl":"10.1159/000547412","url":null,"abstract":"Introduction: Congenital heart defects (CHD) affect approximately 10-12 per 1,000 newborns globally, and they can be divided into simple cardiac defects or severe and complex ones. Its etiology derives from environmental and genetic causes, with 20-30% of cases being genetic conditions ranging from alterations such as aneuploidies, monogenic defects, and copy number variations (CNVs). Even with the severity of this condition, many patients remain with an uncertain diagnosis. This study aimed to evaluate patients with CHD who are still undiagnosed but have already undergone genetic testing and evaluation and provide a guideline that can be followed in third-world countries to make CHD diagnostics faster and easier.Method: DNA was extracted from all patients included; first the samples were analyzed with the P311 multiplex ligation-dependent probe amplification (MLPA) kit specific to CHD, and the patients that remain undiagnostic were analyzed with the P245 MLPA kit for microdeletions.Results: CNVs were identified in 36% of the patients, representing a high detection rate.Conclusion: The patient selection and prior clinical evaluation may explain our high detection rate, as much as the karyotype and fluorescent in situ hybridization normal results used for screening, combined with using two MLPA kits for detection.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253341","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 Rare Case of Bardet-Biedl Syndrome Caused by a Heterozygous Point Variant in BBS7 and a CNV Involved BBS7. 由BBS7杂合点变异和涉及BBS7的CNV引起的罕见Bardet-Biedl综合征病例

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-07-11 DOI: 10.1159/000547307

Xingkun Yang, Xiaoqiang Zhou, Cheng Zhou, Chao Li, Shuijuan Wu, Yasi Zhou, Jiayue Du, Xiaoling Guo, Xiang Huang

{"title":"A Rare Case of Bardet-Biedl Syndrome Caused by a Heterozygous Point Variant in BBS7 and a CNV Involved BBS7.","authors":"Xingkun Yang, Xiaoqiang Zhou, Cheng Zhou, Chao Li, Shuijuan Wu, Yasi Zhou, Jiayue Du, Xiaoling Guo, Xiang Huang","doi":"10.1159/000547307","DOIUrl":"10.1159/000547307","url":null,"abstract":"Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder classified as a multisystem nonmotile ciliopathy, primarily characterized by retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, kidney disease, and abnormalities of hypogonadism and genitourinary.Case presentation: A fetus presenting with enlarged kidneys and enhanced echogenicity was identified during a prenatal screening at 17 weeks of gestation. Genetic analysis of the fetus was performed using chromosomal microarray analysis (CMA) and clinical exome sequencing (CES). The prenatal assessment yielded notable results in the fetus, with CMA and CES analysis detecting a compound heterozygous variant in the BBS7 gene and a substantial deletion in the chromosomal region 4q26q27. Subsequent autopsy findings corroborate the presence of postaxial polydactyly, bilateral renal enlargement, and an accessory auricle in the fetus.Conclusions: Our study expands the range of phenotypes associated with BBS to include bilateral accessory auricle, as well as broadens the spectrum of variants linked to BBS. Our findings support the significant contribution of copy number variants to BBS, offering clinicians valuable insights for diagnosing the condition, particularly in prenatal settings.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253380","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 Treatable Cause of Seizures and Hyperphosphatasia: Patients with PGAP2 and PGAP3 Mutations. 癫痫发作和高磷酸症的可治疗原因：PGAP2和PGAP3突变患者。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-07-09 DOI: 10.1159/000547293

Ezgi Burgac, Merve Yoldas Celik, Burcu Köseci, Habibe Koc Ucar

{"title":"A Treatable Cause of Seizures and Hyperphosphatasia: Patients with PGAP2 and PGAP3 Mutations.","authors":"Ezgi Burgac, Merve Yoldas Celik, Burcu Köseci, Habibe Koc Ucar","doi":"10.1159/000547293","DOIUrl":"10.1159/000547293","url":null,"abstract":"Introduction: Hyperphosphatasia with mental retardation syndrome (HPMRS) is characterized by intellectual impairment, seizures, hypotonia, facial dysmorphism, and elevated serum alkaline phosphatase (ALP) level. HPMRS has been linked to mutations in several genes including PGAP2 and PGAP3. Here, we report 2 patients of HPMRS3 and HPMRS4 and highlight the genetic and phenotypic diversity of this disorder.Case reports: Patient 1, a 1-year-old male with developmental delay, generalized tonic-clonic seizures, and dysmorphic facial features, was found to have a pathogenic variant in the PGAP3 gene. Patient 2, a 1-year-old female with seizures, hypotonia, joint hypermobility, and facial dysmorphism, was found to have a pathogenic variant in the PGAP2 gene. Both patients exhibited elevated ALP levels. Brain MRI of patient 1 revealed periventricular hyperintense signal foci, while patient 2 showed cerebral atrophy and basal ganglia diffusion restriction.Discussion: HPMRS3 and HPMRS4 share clinical features including elevated ALP levels, developmental delay, seizures, and facial dysmorphisms. Although joint hypermobility is not a common feature of HPMRS3, it was observed in our patients. Both patients responded well to high-dose pyridoxine, suggesting a potential therapeutic benefit for seizure management. This report expands the understanding of HPMRS by presenting novel genetic findings and providing insights into the clinical presentation of PGAP2- and PGAP3-related conditions.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253383","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

CRB2-Related Syndrome in 2 New Patients: Three Novel Variants. 2例新患者的crb2相关综合征：三个新变体

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-07-02 DOI: 10.1159/000547159

Ayşe Burcu Doğan Arı, Ayberk Türkyılmaz, Nagihan Çiftçi Pınar, Uğur Turhan, Avni Merter Keçeli, Umut Selda Bayrakçı, Esra Kılıç

{"title":"CRB2-Related Syndrome in 2 New Patients: Three Novel Variants.","authors":"Ayşe Burcu Doğan Arı, Ayberk Türkyılmaz, Nagihan Çiftçi Pınar, Uğur Turhan, Avni Merter Keçeli, Umut Selda Bayrakçı, Esra Kılıç","doi":"10.1159/000547159","DOIUrl":"10.1159/000547159","url":null,"abstract":"Introduction: The Crumbs homolog-2 (CRB2)-related syndrome is an extremely rare genetic disorder characterized by congenital hydrocephalus, steroid-resistant nephrotic syndrome, and cardiac anomalies. It is caused by biallelic variants in the CRB2 gene.Case presentation: Herein, 2 new patients are presented including congenital hydrocephalus, nephrotic syndrome, scimitar syndrome, and severe cardiac anomalies. CRB2-related syndrome was considered with the present clinical findings and whole exome sequencing revealed three novel variants in CRB2 gene. Microcephaly, ventricular hypertrophy, anomalous pulmonary venous return, pulmonary sequestration, and thymus hypoplasia were presented only in the current patients. Variants in exon 2 (c.335G>A, p.Cys112Tyr) and intron 2 (c.419-2A>G) were reported only in the presented report. In addition, the first likely pathogenic splice-site variant was reported in this report.Conclusion: Accurate diagnosis is crucial for increasing clinical awareness and offering genetic counseling to affected families.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745558","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

Long-Term Renal Transplant Success Is Possible in Hypoparathyroidism, Sensorineural Deafness, and Renal Dysplasia Syndrome: A Case Report. 长期肾移植在甲状旁腺功能减退、感音神经性耳聋和肾发育不良综合征中是可能成功的：一例报告。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-07-02 DOI: 10.1159/000546948

Lauren Alvey, Vignesh Viswanath, Joshua W Owens, Amelle Shillington

{"title":"Long-Term Renal Transplant Success Is Possible in Hypoparathyroidism, Sensorineural Deafness, and Renal Dysplasia Syndrome: A Case Report.","authors":"Lauren Alvey, Vignesh Viswanath, Joshua W Owens, Amelle Shillington","doi":"10.1159/000546948","DOIUrl":"10.1159/000546948","url":null,"abstract":"Introduction: Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is caused by haploinsufficient GATA3 variants. Renal disease is present in 72% of patients with HDR syndrome, with a widely variable age of onset and rate of progression. Overall prognosis is primarily dependent upon the severity of renal disease. Four patients have been previously reported to have kidney transplants due to HDR syndrome, but there are minimal data describing transplant outcomes. We describe a case of a 74-year-old male with HDR syndrome receiving a living related renal transplant lasting 27 years.Case presentation: A 74-year-old male with genetically confirmed HDR syndrome due to a pathogenic c.608_609del (p.Gly203Glufs*100) variant in GATA3. He developed hearing loss as an adolescent and was diagnosed with end stage renal disease at age 46. He had a living donor kidney transplant at age 47 that was well tolerated until age 73, and he is now listed for a repeat transplant.Discussion: This individual previously had a clinical diagnosis of Alport syndrome, but the presence of congenital symptoms in other family members suggested an alternative diagnosis. In addition to highlighting discrepancies between Alport syndrome and HDR syndrome, this case establishes that long-term successful renal outcomes are possible in HDR syndrome. Current limited evidence suggests kidney transplantation should be readily offered to individuals with end-stage renal disease due to HDR syndrome.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253317","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 Compound Heterozygous CYP27A1 Variant in Cerebrotendinous Xanthomatosis: A Case Report from a Non-Consanguineous Family. 脑腱黄瘤病中一种新的复合杂合CYP27A1变异：来自一个非近亲家庭的病例报告。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-06-23 DOI: 10.1159/000547016

Hande Nur Cesur Baltacı, Burcu Sağlam Ada, Nüket Yürür Kutlay, Ajlan Tükün, Serap Tıraş Teber, Turgay Coşkun

{"title":"A Novel Compound Heterozygous CYP27A1 Variant in Cerebrotendinous Xanthomatosis: A Case Report from a Non-Consanguineous Family.","authors":"Hande Nur Cesur Baltacı, Burcu Sağlam Ada, Nüket Yürür Kutlay, Ajlan Tükün, Serap Tıraş Teber, Turgay Coşkun","doi":"10.1159/000547016","DOIUrl":"10.1159/000547016","url":null,"abstract":"Introduction: Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive lipid storage disorder characterized by the accumulation of cholesterol and cholestanol in various tissues. It is caused by pathogenic variants in the CYP27A1 gene, which encodes the mitochondrial enzyme sterol 27-hydroxylase.Case presentation: Here, we present an 8-year-old boy with attention-deficit/hyperactivity disorder, born to non-consanguineous parents. He was referred to our center for CYP27A1 gene analysis and genetic counseling, following the identification of a homozygous deletion in exon 6 of the CYP27A1 gene in his mother. His plasma cholestanol levels were also elevated, supporting a diagnosis of CTX. The proband's father had a history of epilepsy and mild intellectual disability. Genetic analysis of the father revealed a novel heterozygous p.(Glu170Valfs*16) variant in the CYP27A1 gene. Based on these findings, the proband was found to carry a compound heterozygous variant in CYP27A1, confirming the molecular diagnosis of CTX. After genetic counseling, treatment with chenodeoxycholic acid (CDCA) was initiated. Plasma cholestanol levels normalized, and some clinical symptoms showed improvement after 2 months of treatment.Conclusions: Early genetic screening of presymptomatic family members is critical, as timely initiation of CDCA therapy can prevent or significantly attenuate the clinical progression of CTX.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253314","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

Erratum. 勘误表。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-06-19 DOI: 10.1159/000546546

引用次数: 0

Pamidronate Treatment of a Patient with Opsismodysplasia and a Novel INPPL1 Variant: Efficacy, Mechanism, and Clinical Outcomes. 帕米膦酸盐治疗Opsismodysplasia患者和一种新的INPPL1变异：疗效、机制和临床结果。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-06-03 DOI: 10.1159/000546324

Gulin Tabanli, Filiz Hazan, Gulsen Ozer, Ozge Koprulu, Ozlem Nalbantoglu, Behzat Ozkan

引用次数: 0

A Novel SON Gene Variant Associated with Rare Clinical Features in ZTTK Syndrome: A Case Report and Literature Review. 一种与ZTTK综合征罕见临床特征相关的SON基因新变异：1例报告及文献复习。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2025-05-28 DOI: 10.1159/000546621

Kubra Ates, Murat Ozturk, Zeynep Esener, Ahmet Sigirci, Ibrahim Tekedereli

{"title":"A Novel SON Gene Variant Associated with Rare Clinical Features in ZTTK Syndrome: A Case Report and Literature Review.","authors":"Kubra Ates, Murat Ozturk, Zeynep Esener, Ahmet Sigirci, Ibrahim Tekedereli","doi":"10.1159/000546621","DOIUrl":"10.1159/000546621","url":null,"abstract":"Introduction: Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare multisystemic congenital disorder caused by SON gene variants. This study aimed to present the results of whole exome sequencing, and describe some rare findings observed in the proband.Case presentation: An 11-year-old boy exhibited hypotonia, poor growth, short stature, and microcephaly. The patient displayed various neurological symptoms, such as developmental delay, seizures, hydrocephalus, and brain abnormalities. He presented with strabismus, urinary problems, and facial dysmorphism. A history of stroke, obsession, insomnia, self-injurious behavior, and hearing loss was also noted. Based on the patient's clinical findings, whole exome sequencing was performed. A novel variant in the SON gene was identified. This variant was confirmed by Sanger sequencing. Notably, the parents tested normal for the variant.Conclusion: This study presents a patient who exhibited a wide range of behavioral abnormalities, stroke, and recurrent urolithiasis - features that are rarely reported in ZTTK syndrome - and includes a review of the literature.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601971","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