Molecular Syndromology最新文献_第8页

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 : 2026-04-01 Epub 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":"179-185"},"PeriodicalIF":0.9,"publicationDate":"2026-04-01","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

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 : 2026-04-01 Epub 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":"174-178"},"PeriodicalIF":0.9,"publicationDate":"2026-04-01","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 : 2026-04-01 Epub 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":"154-159"},"PeriodicalIF":0.9,"publicationDate":"2026-04-01","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

HIRA, NKX2-5, and GATA4 Alterations versus Cardiac Malformations Related to 22q11.2 Deletion Syndrome. HIRA、NKX2-5和GATA4改变与22q11.2缺失综合征相关的心脏畸形

IF 0.8 4区医学

Molecular Syndromology Pub Date : 2026-04-01 Epub Date: 2025-06-10 DOI: 10.1159/000546625

Bruna Lixinski Diniz, Desirée Deconte, Ana Kalise Böttcher, Rafaela Mergener, Bruna Baierle Guaraná, Natasha Malgarezi de Moraes, Rafael Fabiano Machado Rosa, Paulo Ricardo Gazzola Zen

{"title":"HIRA, NKX2-5, and GATA4 Alterations versus Cardiac Malformations Related to 22q11.2 Deletion Syndrome.","authors":"Bruna Lixinski Diniz, Desirée Deconte, Ana Kalise Böttcher, Rafaela Mergener, Bruna Baierle Guaraná, Natasha Malgarezi de Moraes, Rafael Fabiano Machado Rosa, Paulo Ricardo Gazzola Zen","doi":"10.1159/000546625","DOIUrl":"10.1159/000546625","url":null,"abstract":"Introduction: Congenital heart disease (CHD) comprises a wide spectrum of structural defects. However, the etiology of a large proportion of CHDs remains undefined. Among the genetic causes, 22q11.2 deletion syndrome is the condition which most stands out. This association is related to many cardiac embryonic development genes being in the chromosome 22 region, as well as being a region with a high probability of errors in gene recombination, influencing normal levels of gene expression and affecting a gene's copy number.Objective: This study aimed to compare molecular findings using multiplex ligation-dependent probe amplification assay in patients presenting CHD with a previous fluorescence in situ hybridization (FISH) diagnosis of 22q11.2DS versus patients without known genetic disorder.Results: All patients had CHD and facial dysmorphia. Patients who had been previously diagnosed by FISH were found to have the exact same deletion size, low-copy-number repeat sequences and genes involved. GATA4 when deleted or duplicated in different exons (1 and 6) showed distinct congenital heart defect phenotypes. Patients who did not have their diagnosis defined by FISH showed different molecular results, ranging from normal findings to alterations in the GATA and NXK2 genes.Conclusion: Molecular diversity in cardiac malformations is a reality and a great challenge since genotype-phenotype correlation is hindered. Therefore, new insights on that matter should be considered: 22q11.2 deletion syndrome should only be linked to the chromosome 22 region or is there a phenotype variability to be looked at that involves a broader genomic environment?","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"17 2","pages":"112-122"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13046320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624166","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 New Family with X-Linked Intellectual Disability 90: A Case Report of a Novel DLG3 Variant and Literature Review. 一个新家族的x连锁智力残疾90：一个新的DLG3变异的病例报告和文献复习。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2026-04-01 Epub Date: 2025-05-20 DOI: 10.1159/000546429

Ceren Alavanda, Kısmet Çıkı

{"title":"A New Family with X-Linked Intellectual Disability 90: A Case Report of a Novel DLG3 Variant and Literature Review.","authors":"Ceren Alavanda, Kısmet Çıkı","doi":"10.1159/000546429","DOIUrl":"10.1159/000546429","url":null,"abstract":"Introduction: X-linked intellectual disability (XLID) is a highly heterogeneous disease. Apart from Fragile X, other diseases that cause XLID are quite rare. The DLG3 gene variants cause XLID90.Case presentation: This study presents 2 patients diagnosed with XLID90 after identifying a novel variant in the DLG3 gene through whole exome sequencing analysis. Both patients had autism spectrum disorder, intellectual disability, and dysmorphism. Additionally, an arachnoid cyst, which has not been previously reported in XLID90, was also detected in the patients. XLID90 has neither specific clinical findings nor dysmorphic features. Therefore, a detailed literature review is essential for clearly elucidating the phenotype. Here, one hundred and two XLID90 cases from 18 publications reporting pathogenic variants in the DLG3 gene were reviewed to investigate the detailed clinical findings among these patients. The literature review has shown that ID is more frequently observed in patients with truncating variants, while seizures are more commonly seen in patients with non-truncating variants.Conclusion: This study will provide homogeneous healthcare to patients and allow for appropriate genetic counseling.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"135-141"},"PeriodicalIF":0.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144974702","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 : 2026-04-01 Epub 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":"160-168"},"PeriodicalIF":0.9,"publicationDate":"2026-04-01","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

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 : 2026-04-01 Epub 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":"142-153"},"PeriodicalIF":0.9,"publicationDate":"2026-04-01","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

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 : 2026-04-01 Epub 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":"186-190"},"PeriodicalIF":0.9,"publicationDate":"2026-04-01","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

Focal Dermal Hypoplasia with Unusual Cardiac Anomalies Presentation: A Report of Two Cases and Literature Review. 局灶性皮肤发育不全伴异常心脏异常2例报告并文献复习。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2026-04-01 Epub Date: 2025-04-02 DOI: 10.1159/000545533

Nagehan Bilgeç, Mahmut Gökdemir, Özgür Balasar, Fayize Maden Bedel, Hüseyin Çaksen

{"title":"Focal Dermal Hypoplasia with Unusual Cardiac Anomalies Presentation: A Report of Two Cases and Literature Review.","authors":"Nagehan Bilgeç, Mahmut Gökdemir, Özgür Balasar, Fayize Maden Bedel, Hüseyin Çaksen","doi":"10.1159/000545533","DOIUrl":"10.1159/000545533","url":null,"abstract":"Introduction: Focal dermal hypoplasia (FDH), also known as Goltz syndrome, is an exceedingly rare multisystemic disease with X-linked dominant inheritance involving meso-ectodermal tissues. FDH is characterized by specific cutaneous lesions, ectodermal findings, craniofacial abnormalities, ocular malformations, and limb deformities. Congenital diaphragmatic hernia, urinary anomalies, heart anomalies, lung defects, or central nervous system malformations rarely accompany it.Case presentation: We report 2 patients with focal dermal hypoplasia with concurrent cardiac findings and PORCN variants. In the first case, hemitruncus, an aortic arch, severe isthmus hypoplasia, and pulmonary arterial hypertension were observed. In the second case, a secundum-type atrial septal defect was observed.Conclusion: Genotype-phenotype correlations are limited in the literature. We aimed to establish the genotype-phenotype relationship of the novel variants detected and better understand the correlation between the clinical features of focal dermal hypoplasia and the Wnt signaling mechanism.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"191-204"},"PeriodicalIF":0.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144100","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 Intragenic Duplication of CREBBP in Rubinstein-Taybi Syndrome: A Case Report Expanding the Genotype-Phenotype Spectrum. Rubinstein-Taybi综合征中一种新的CREBBP基因内重复：一个扩大基因型-表型谱的病例报告。

IF 0.9 4区医学

Molecular Syndromology Pub Date : 2026-04-01 Epub Date: 2025-08-21 DOI: 10.1159/000547120

Enes Dursun, Eyyup Uctepe, Serhat Guler, Hanifenur Mancilar, Ahmet Yesilyurt

{"title":"A Novel Intragenic Duplication of CREBBP in Rubinstein-Taybi Syndrome: A Case Report Expanding the Genotype-Phenotype Spectrum.","authors":"Enes Dursun, Eyyup Uctepe, Serhat Guler, Hanifenur Mancilar, Ahmet Yesilyurt","doi":"10.1159/000547120","DOIUrl":"10.1159/000547120","url":null,"abstract":"Introduction: Rubinstein-Taybi syndrome (RSTS) is most often caused by loss-of-function variants in CREBBP; intragenic duplications are rare and extremely under-recognized.Case presentation: We describe a 5-year-old girl with global developmental delay, intellectual disability, frontal bossing, upslanted palpebral fissures, broad angulated halluces, and scoliosis. Whole-exome sequencing with copy number analysis revealed a heterozygous de novo duplication of approximately 13 kb encompassing exons 7-16 of CREBBP (NM_004380.3). Multiplex ligation-dependent probe amplification confirmed the duplication in the proband and excluded it in both parents. The event is predicted to introduce a frameshift, leading to premature truncation. No additional pathogenic variants were detected.Conclusion: This is the first reported CREBBP duplication spanning exons 7-16, expanding the mutational spectrum of RSTS and illustrating that intragenic duplications can manifest with a partially atypical craniofacial profile. The case underscores the value of incorporating high-resolution copy number interrogation into RSTS workflows when single nucleotide variant analysis is uninformative and supports systematic deposition of such variants to refine genotype-phenotype correlations.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"169-173"},"PeriodicalIF":0.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253377","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