Case Reports in Genetics最新文献

A Novel Case of NOTCH1 Variant and Nonimmune Hydrops Fetalis: A Case Report. NOTCH1变异和非免疫性水肿胎儿1例报告。

Case Reports in Genetics Pub Date : 2025-09-01 eCollection Date: 2025-01-01 DOI: 10.1155/crig/6865742

Genevieve R Mazza, Alesandra R Rau, Madushka Y De Zoysa

{"title":"A Novel Case of NOTCH1 Variant and Nonimmune Hydrops Fetalis: A Case Report.","authors":"Genevieve R Mazza, Alesandra R Rau, Madushka Y De Zoysa","doi":"10.1155/crig/6865742","DOIUrl":"10.1155/crig/6865742","url":null,"abstract":"Nonimmune hydrops fetalis (NIHF) refers to the pathologic accumulation of fluid within the fetus due to causes other than red cell alloimmunization and now accounts for up to 90% of fetal hydrops cases. Fetal hydrops is associated with significant morbidity and mortality, and the exact prognosis is largely dependent on the underlying etiology. The most common etiologies include cardiovascular causes and chromosomal or genetic abnormalities. Despite this, diagnostic testing with karyotype or chromosomal microarray only identifies approximately 25% of cases, and up to 20% of cases remain idiopathic or unknown. We report the first known case of NIHF related to a NOTCH1 pathogenic variant. In this case, NIHF was diagnosed at 30 weeks' gestation in a fetus with low-risk prenatal genetic screening, noncontributory anatomic survey, and normal chromosomal microarray. The hydrops was uniquely localized to scalp edema and pleural effusions requiring bilateral thoracentesis and never progressed to involve pericardial effusion or ascites. Whole exome sequencing diagnosed a novel pathogenic variant in the NOTCH1 gene. This is the first reported case of NIHF in the setting of NOTCH1 pathogenic variant and is an important addition to the existing literature on this incredibly diverse, high-risk pathology.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2025 ","pages":"6865742"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Unexpected Case of Somatic Mosaicism of the Dutch p16-Leiden Founder Variant in the CDKN2A Gene. CDKN2A基因荷兰p16-Leiden始创变异体嵌合体的意外案例。

Case Reports in Genetics Pub Date : 2025-08-28 eCollection Date: 2025-01-01 DOI: 10.1155/crig/6261903

M van der Meulen, J T van Wezel, D Terlouw, J Morreau, E M P Steeghs, R van Doorn, M E van Leerdam, A M Onnekink, M C de Ruiter, N van der Stoep, T P Potjer

{"title":"An Unexpected Case of Somatic Mosaicism of the Dutch p16-Leiden Founder Variant in the CDKN2A Gene.","authors":"M van der Meulen, J T van Wezel, D Terlouw, J Morreau, E M P Steeghs, R van Doorn, M E van Leerdam, A M Onnekink, M C de Ruiter, N van der Stoep, T P Potjer","doi":"10.1155/crig/6261903","DOIUrl":"10.1155/crig/6261903","url":null,"abstract":"CDKN2A is the primary high-risk predisposition gene for familial cutaneous melanoma. In the Netherlands, most carriers of pathogenic germline variants in CDKN2A harbor a unique, population-specific founder variant, c.225_243del, commonly referred to as p16-Leiden. For decades, this distinctive 19 base-pair deletion in CDKN2A had been identified exclusively as a germline variant. Here, we report an exceptional case of somatic mosaicism for the p16-Leiden variant in an Irish male with a concurrent diagnosis of Kartagener's syndrome but no history of malignancy. The variant was first identified through targeted next-generation sequencing (NGS) of a fundic gland polyp in the distal esophagus, showing a variant allele frequency (VAF) of 40%. Subsequent analysis also detected the variant in the patient's buccal swab DNA (VAF 0.3%), while it was notably absent in multiple other tissue samples, including blood, urine, skin, and several additional samples from the proximal gastrointestinal tract. We explore several hypotheses that could explain these intriguing findings.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2025 ","pages":"6261903"},"PeriodicalIF":0.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Infant Born With Autosomal Recessive Glycogen Storage Disease Type IV due to Complete Maternal Isodisomy of Chromosome 3. 由于母体3号染色体完全同位体导致的常染色体隐性隐性糖原储存病IV型新生儿。

Case Reports in Genetics Pub Date : 2025-08-27 eCollection Date: 2025-01-01 DOI: 10.1155/crig/5577571

Sigrid Skovby Olsen, Anja Ernst, Pia Sønderby Christensen, Ellen Dagmar Björnsdóttir, Lasse Ringsted Mark, Albert Vejlin Stefansen, Allan Thomas Højland

引用次数: 0

Chromosome 1p31.1 Deletion: A Case With Developmental Delay, Hypotonia, Cryptorchidism, Abnormal Oral Frenulum, and Feet Deformity. 染色体1p31.1缺失：发育迟缓、张力低下、隐睾、口系带异常、足部畸形1例。

Case Reports in Genetics Pub Date : 2025-07-27 eCollection Date: 2025-01-01 DOI: 10.1155/crig/6152118

Tatiana Mikhailova, Ria Garg

{"title":"Chromosome 1p31.1 Deletion: A Case With Developmental Delay, Hypotonia, Cryptorchidism, Abnormal Oral Frenulum, and Feet Deformity.","authors":"Tatiana Mikhailova, Ria Garg","doi":"10.1155/crig/6152118","DOIUrl":"10.1155/crig/6152118","url":null,"abstract":"Deletions within the chromosomal locus 1p31.1 are rare, with only a limited number of documented cases. The typical clinical presentation includes intellectual disability, failure to thrive, and craniofacial abnormalities. Some cases may also present with cardiac, gastrointestinal, and genitourinary malformations. Variability in deletion size contributes to a broad spectrum of clinical phenotypes, and a comprehensive understanding of the syndrome's manifestations is still evolving. This case study aims to provide additional insights into 1p31.1 microdeletion syndrome, enhancing knowledge of its genetic and phenotypic characteristics to improve recognition by clinicians. Here, we report a case featuring a 14.385 Mb deletion isolated to the 1p31.1 region, encompassing 41 genes. The deletion manifested with microcephaly, distinctive facial morphology, hypotonia, developmental delay, bilateral cryptorchidism, and flat feet. Notably, our case also exhibited congenital thickening of the lingual and labial frenulum, a trait not typically associated with this deletion.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2025 ","pages":"6152118"},"PeriodicalIF":0.0,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12318624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "A Fatal Case of 3-Hydroxyisobutyryl-CoA Hydrolase Deficiency in a Term Infant With Severe High Anion Gap Acidosis and Review of the Literature". “严重高阴离子间隙酸中毒足月婴儿3-羟基异丁基辅酶A水解酶缺乏致死性病例及文献复习”的更正。

Case Reports in Genetics Pub Date : 2025-07-25 eCollection Date: 2025-01-01 DOI: 10.1155/crig/9827627

引用次数: 0

Paternal UPD (15) With Disease-Causing Mutation and Small Supernumerary Ring Chromosome 15: A Case Report. 父系UPD（15）伴致病突变和小多余环染色体15：一例报告。

Case Reports in Genetics Pub Date : 2025-07-25 eCollection Date: 2025-01-01 DOI: 10.1155/crig/4973753

David Lee Curtis, Nasim Bekheirnia, Lorraine Potocki, Ludmila Matyakhina, Mir Reza Bekheirnia

引用次数: 0

A Rare Case of Neonatal Cholestasis Linked to FOCAD Gene Variants: Exploring the Variable Phenotypic Presentation and Its Implications. 一例罕见的与FOCAD基因变异相关的新生儿胆汁淤积症：探讨其可变表型表现及其意义。

Case Reports in Genetics Pub Date : 2025-07-01 eCollection Date: 2025-01-01 DOI: 10.1155/crig/9569160

Ariel Tarrell, Jessika Weber, Reem Shawar, Luca Brunelli, Susan Morelli, Pinar Bayrak-Toydemir, Elizabeth Doughty, Gulsen Akay, Lorenzo D Botto, Emily Flemming, N Scott Reading, Catalina Jaramillo

引用次数: 0

Pathogenic Deep Intronic Variant in CNGB3 Identified From Whole-Genome Sequencing in an Unsolved Case of Patient Affected With Achromatopsia. 从一例色盲患者的全基因组测序中鉴定出CNGB3致病性深内含子变异。

Case Reports in Genetics Pub Date : 2025-05-27 eCollection Date: 2025-01-01 DOI: 10.1155/crig/3466358

Matthew R Gregory, Khurram Liaqat, Kayla Treat, Kathryn M Haider, Francesco Vetrini, Erin Conboy

{"title":"Pathogenic Deep Intronic Variant in CNGB3 Identified From Whole-Genome Sequencing in an Unsolved Case of Patient Affected With Achromatopsia.","authors":"Matthew R Gregory, Khurram Liaqat, Kayla Treat, Kathryn M Haider, Francesco Vetrini, Erin Conboy","doi":"10.1155/crig/3466358","DOIUrl":"10.1155/crig/3466358","url":null,"abstract":"Achromatopsia (ACHM) (MIM: 262300) is an autosomal recessive disorder characterized by reduced visual acuity and color blindness. In this report, we review the case of a 14-year-old male patient diagnosed with achromatopsia with a history of retinal dystrophy, cone dysfunction with normal dark-adapted response on ERG, congenital nystagmus, farsightedness, and astigmatism. The diagnostic exome sequencing previously revealed a single maternally inherited pathogenic CNGB3 variant (c.1148delC, p.(T383lfs∗13). Following enrollment in the Undiagnosed Rare Disease Clinic (URDC) at Indiana University School of Medicine (IUSM), genome sequencing (GS) identified a second CNGB3 known variant c.1663-1205G > A p.(Gly555Leufs∗33), which was classified as likely pathogenic. Identification of this variant in the patient provided the evidence needed for a molecular diagnosis and ended a 15-year diagnostic odyssey for the patient and his family. With a diagnosis, the patient is eligible for gene therapy and qualifies for the state-run Vocational Rehabilitation Program and bioptic driving.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2025 ","pages":"3466358"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 NPHP5 Gene Mutation in Three Siblings With Nephronophthisis Without Retinitis Pigmentosa: A Case Report. 一个新的NPHP5基因突变在三个兄弟姐妹肾病无视网膜色素变性：1例报告。

Case Reports in Genetics Pub Date : 2025-04-28 eCollection Date: 2025-01-01 DOI: 10.1155/crig/1453255

Randah Abdullah Dahlan, Roaa Hani Fairoozy

{"title":"A Novel NPHP5 Gene Mutation in Three Siblings With Nephronophthisis Without Retinitis Pigmentosa: A Case Report.","authors":"Randah Abdullah Dahlan, Roaa Hani Fairoozy","doi":"10.1155/crig/1453255","DOIUrl":"https://doi.org/10.1155/crig/1453255","url":null,"abstract":"Nephronophthisis (NPHP) is a hereditary renal disorder characterized by the progression to end-stage renal disease (ESRD) at a young age. Our understanding of this disorder continues to improve as we identify more genes and gene variants associated with NPHP. In this report, we present a young patient with newly diagnosed advanced renal impairment and a strong family history of ESRD at a young age. The patient's kidney biopsy showed features suggestive of severe chronic interstitial nephritis, along with histopathological findings of advanced renal disease. Genetic testing revealed a novel variant in the IQCB1/NPHP5 gene, which is autosomal recessive. Family genetic analysis revealed that the patient's parents and two of his children are heterozygous for the identified variant, while two siblings with ESRD are homozygous for the IQCB1 p.(Ala486Asp) variant. Unlike previously described mutations in the IQCB1/NPHP5 gene, the patient and his affected siblings do not have retinitis pigmentosa. We report this novel gene variant in a Saudi family, describe its associated clinical features, and present the results of the family segregation analysis.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2025 ","pages":"1453255"},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual Diagnosis of Fragile X Syndrome and DEPDC5-Related Disorder Emphasizes DEPDC5's Role Beyond Familial Epilepsy: A Case Report and Literature Review. 脆性X综合征和DEPDC5相关疾病的双重诊断强调了DEPDC5在家族性癫痫之外的作用：1例报告和文献复习

Case Reports in Genetics Pub Date : 2025-04-02 eCollection Date: 2025-01-01 DOI: 10.1155/crig/4501466

Rory Edwards, Grace Murphy, Joshua W Owens, Craig Erickson, Robert Hopkin, Amelle Shillington

{"title":"Dual Diagnosis of Fragile X Syndrome and DEPDC5-Related Disorder Emphasizes DEPDC5's Role Beyond Familial Epilepsy: A Case Report and Literature Review.","authors":"Rory Edwards, Grace Murphy, Joshua W Owens, Craig Erickson, Robert Hopkin, Amelle Shillington","doi":"10.1155/crig/4501466","DOIUrl":"https://doi.org/10.1155/crig/4501466","url":null,"abstract":"Dep domain-containing Protein 5 (DEPDC5), encoded by the gene DEPDC5, regulates the cell cycle by inhibiting the mTORC1 pathway in response to amino acid deficiency. Loss of function DEPDC5 variants are recognized to present as focal familial epilepsy; however, associations with comorbid brain malformations and neurodevelopmental disorders have also been reported. mTOR inhibitors were found to benefit DEPDC5-knockout mice. Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder caused by loss of function of FMR1, and females are expected to have milder neurodevelopmental presentations than males. The reported individual is a 17-year-old female diagnosed with FXS at 1 year of age, but the severity of her neuropsychiatric symptoms prompted further genetic testing at age 14, revealing a likely pathogenic c.4307_4310del DEPDC5 variant. Following this diagnosis, she was started on the mTOR inhibitor sirolimus without significant clinical response. She has never been diagnosed with epilepsy; however, her DEPDC5 and FXS dual diagnosis was thought explanatory for her presentation. A review of 213 previously reported individuals with DEPDC5-related disorder demonstrated that 15.2% of individuals do not have epilepsy, 24.3% have intellectual disability, and 33.8% have brain malformations. Her lack of response to sirolimus may represent the presence of a critical treatment window for mTOR inhibitors in neurodevelopmental disorders.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2025 ","pages":"4501466"},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11981699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0