Case Reports in Genetics最新文献

{"title":"A Rare Case of Concurrent SNRPB Mutation and 22q11.2 Microduplication in a Child With Cerebro-Costo-Mandibular Syndrome.","authors":"Elizabeth Slear, Claire Thompson, Virginia Ruas","doi":"10.1155/crig/4169170","DOIUrl":"10.1155/crig/4169170","url":null,"abstract":"<p><p>We present a unique case of an infant born with both a microduplication of 22q11.2 and SNRPB gene mutations suggestive of cerebro-costo-mandibular syndrome (CCMS). Microduplications of 22q11 are known to present with a variety of phenotypes ranging from asymptomatic to significant physical and mental health challenges. CCMS is a rare autosomal dominant condition caused by a mutation in the SNRPB gene and typically presents with posterior rib malformations and branchial arch deformities. There have been less than 100 reported cases of CCMS in the literature, and this may be the first documented case of a patient with both CCMS and a 22q11 microduplication.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"4169170"},"PeriodicalIF":0.0,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12917849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272062","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}

{"title":"Three Unrelated Children With Childhood Apraxia of Speech: Exome Sequencing and Functional Gene Analysis Imply a Role of Laminin-511 in Early Neurodevelopment.","authors":"Caitlin Raaz, Laurel Bruce, Madhavi Ganapathiraju, Judith Klein-Seetharaman, Li Liu, Valentin Dinu, Marjan Chapi, Eunhyo Kim, Yookyung Kim, Tiffanie White, Beate Peter","doi":"10.1155/crig/9927839","DOIUrl":"10.1155/crig/9927839","url":null,"abstract":"<p><p>Childhood apraxia of speech (CAS) is characterized by motor discoordination in the speech domain and also in fine and gross motor systems, implicating the early developing cerebellum. Comorbidity with autism spectrum disorder (ASD) and other neurodevelopmental conditions has been observed. The genetic etiology is highly heterogeneous. Here, we present three unrelated individuals with CAS and concomitant fine and gross motor involvement but different genetic variants of interest. The DNA of the cases and their parents underwent exome sequencing and variant filtering. Using publicly available data, the genes of interest derived from the variants were investigated for expression rates in the early developing brain. Known and putative protein-protein interactions among the genes of highest confidence were identified. Of 28 variants in 28 different genes, variants with highest confidence were situated in <i>FOXN4</i>, <i>LAMA5</i>, <i>LAMB1</i>, <i>LRRK2</i>, and <i>USP17L2</i>. High gene expression rates in the developing cerebellum were observed for <i>LAMA5</i> and <i>LAMB1</i>. These genes encode the α5 and β1 subunits, respectively, of the heterotrimeric extracellular laminin-511 complex, a major component of the basal membrane in many tissues. Network analysis of the five high-confidence genes required expansion with only one additional gene, <i>CDK6</i>, to arrive at a fully connected network. The addition of four genes and inclusion of transcriptional regulation as an additional edge type allowed connecting all 28 genes of interest to arrive at a dense connectome with 32 nodes and 73 edges, representing a network enrichment with <i>p</i> value of < 0.001, suggesting that our network has significantly more interactions than expected under random conditions. We conclude that high levels of genetic heterogeneity converge on a functional gene network governed by stimulation of cells through laminin-511 with shared direct or regulatory expression in the developing cerebellum and phenotypic overlaps of CAS, ASD, and other neurodevelopmental disorders.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"9927839"},"PeriodicalIF":0.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202837","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}

{"title":"Hereditary Myopathy With Early Respiratory Failure Associated With an Incidental <i>COL4A5</i> Variant: A Case Report.","authors":"Ursula Abu Nahla, Rahaf Bleibel, Mai Arafeh, Saif Khaled Abdalhadi Azzam, Lina Barhoum, Mostafa Ibraheem, Motaz Altamimi, Bashar Sultan, Orwa Al Fallah","doi":"10.1155/crig/1630468","DOIUrl":"10.1155/crig/1630468","url":null,"abstract":"<p><strong>Background: </strong>Hereditary myopathy with early respiratory failure (HMERF) is a rare autosomal dominant disorder caused by <i>TTN</i> variants. <i>COL4A5</i> mutations are linked to X-linked Alport syndrome.</p><p><strong>Case presentation: </strong>A 34-year-old male developed progressive lower limb weakness, gait disturbance, nocturnal hypoventilation, and calf hypertrophy. Family history revealed similar symptoms in his mother and sister. Examination showed absent reflexes; MRI demonstrated muscle atrophy and fatty replacement; needle electromyography (EMG) was performed and showed findings consistent with advanced myopathy; however, it was not used as a primary diagnostic tool. Whole-exome sequencing identified a pathogenic <i>TTN</i> variant (c.95126C > G, p.Pro31709Arg), confirming HMERF. A hemizygous <i>COL4A5</i> variant (c.4891C > T, p.Arg1631Cys) was also detected but lacked clinical correlation.</p><p><strong>Discussion and conclusion: </strong>This case illustrates a classic HMERF phenotype confirmed genetically, with an incidental <i>COL4A5</i> variant of uncertain significance. It underscores the importance of genomic testing in atypical neuromuscular presentations and the need for cautious interpretation of incidental findings.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"1630468"},"PeriodicalIF":0.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12890873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182746","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}

{"title":"First Thai Case of Lethal Desbuquois Dysplasia Type I Caused by Novel Compound Heterozygous <i>CANT1</i> Mutations: Expanding the Molecular Spectrum.","authors":"Supitcha Thamissarakul, Teeraphorn Boonswang, Sethapong Lertsakulbunlue, Siriluk Khumsui, Boonchai Boonyawat","doi":"10.1155/crig/9550632","DOIUrl":"10.1155/crig/9550632","url":null,"abstract":"<p><p>Desbuquois dysplasia Type 1 (DBQD1) is an extremely rare autosomal recessive skeletal dysplasia characterized by severe short stature, joint laxity, distinct facial dysmorphism, and advanced carpotarsal ossification. Here, we report the first Thai patient diagnosed with classical lethal DBQD1. A 38-week male infant presented with multiple dysmorphic features, micromelia, joint dislocations, narrow thorax, and respiratory insufficiency leading to death at seven months of age. Radiographic findings revealed hallmark features, including a \"Swedish key\" appearance of the proximal femur and characteristic hand and foot anomalies. Whole exome sequencing identified compound heterozygous missense variants of c.505G > <i>A</i> (p.Asp169Asn) and c.1028G > <i>T</i> (p.Gly343Val) in the <i>CANT1</i> gene. The 3D structural modeling revealed that both variants reside in conserved regions, with predicted effects on calcium binding and protein folding, resulting in impaired enzymatic function and proteoglycan synthesis. Genetic counseling was provided to the family, and prenatal or preimplantation genetic diagnosis was discussed as an option for future pregnancies. Our report expands the mutational spectrum of the <i>CANT1</i> gene, contributing to a better understanding of DBQD1's clinical and molecular presentation, particularly in Southeast Asian populations.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"9550632"},"PeriodicalIF":0.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12887226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167081","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}

{"title":"The Ketogenic Diet in the Neonatal Intensive Care Setting: The Case of a Preterm Newborn With Mitochondrial DNA Depletion Syndrome Type 13 (MTDPS13).","authors":"Gabriele D'Amato, Mattia Gentile, Rossella Carella, Antonio Giannini, Maria Felicia Faienza, Albina Tummolo","doi":"10.1155/crig/6492770","DOIUrl":"10.1155/crig/6492770","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial DNA depletion syndrome 13 (MTDPS13) is an autosomal recessive disorder presenting in early infancy with encephalopathy, hypotonia, lactic acidosis, and severe global developmental delay. Patient-derived cells typically exhibit impaired mitochondrial oxidative phosphorylation and a marked reduction in mitochondrial DNA (mtDNA) copy number.</p><p><strong>Case report: </strong>We report the case of a male preterm neonate born at 31 + 3 weeks of gestation following a pregnancy marked by severe polyhydramnios. At birth, his weight was 1400 g. Physical examination revealed dysmorphic features, redundant and lax skin, and generalized muscular hypotonia. Laboratory investigations showed marked lactic acidosis associated with lactic aciduria, ketonuria, and urinary biomarkers indicating activation of preoxidative phosphorylation biochemical pathways to sustain ATP production. Echocardiography demonstrated mild, early-onset hypertrophic cardiomyopathy. <b>The Exome Analysis Clinical and Biochemical Markers:</b> The exome analysis, performed within the first week of life, highlighted a pathogenic variant in homozygous state of <i>FBXL4</i> gene (c.1648_1649delGA), which led to the diagnosis of MTDPS13. In this clinical contest, a ketogenic diet (KD) was started with a daily caloric intake of 120 kcal/kg and an initial ketogenic ratio of 1:1. These intakes were administered both with a parenteral nutrition and continuous nasogastric tube feeding and were gradually increased and adapted on a day-by-day basis according to lactic acidosis, growth increase, and common metabolic parameters such as glucose, electrolytes, creatinine, and blood urea nitrogen. After 3 days of this treatment approach, a significant reduction in lactate levels and improvement in acid-base balance and growth trend were observed along with clinical and cardiovascular parameters. At discharge from neonatal intensive care unit, the KD was continued at home and during follow-up. The infant showed stability in the clinical and biochemical markers.</p><p><strong>Conclusions: </strong>This is the first documented report of the use of a KD in a preterm neonate with this mitochondrial disorder during the early days of life. Prompt genetic confirmation and early initiation of KD may enable a more targeted and effective management of MTDPS within the neonatal intensive care setting.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"6492770"},"PeriodicalIF":0.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114432","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}

{"title":"Concomitant Chromosomal and Molecular Aberrations in Trisomy 8 Mosaicism and Associated Compound Phenotypes: Report of Three Cases and Review of Literature.","authors":"Zakia Abdelhamed, Daniel Dykas, Autumn DiAdamo, Hongyan Chai, Deqiong Ma, Michele Spencer-Mazon, Yong-Hui Jiang, Jiadi Wen, Allen Bale, Peining Li, Hui Zhang","doi":"10.1155/crig/4494577","DOIUrl":"10.1155/crig/4494577","url":null,"abstract":"<p><p>Trisomy 8 mosaicism (T8M) syndrome is a rare aneuploidy condition affecting 1/25,000-50,000 live births. Affected individuals have highly variable phenotypes from very mild dysmorphism to severe structural anomalies caused by chromosomal mosaicism and possibly undetected molecular aberrations. The utilization of chromosome microarray analysis (CMA) and exome sequencing (ES) in clinical laboratories enable the identification of genomic copy number imbalances and pathogenic gene variants. We presented one patient with a double aneuploid mosaic pattern of Monosomy X and Trisomy 8 for a compound phenotype of Turner syndrome (TS) and T8M syndrome, the second patient with T8M and a mosaic pathogenic variant in the <i>PTEN</i> gene detected by ES, and the third patient with typical phenotypic constellation of malformations with no other genetic aberrations detected by CMA and ES. Classification of mosaic findings was provided using a recommended six-attribute scheme. Review of the literature summarized cases of T8M with concomitant molecular defects of a deletion at 22q11.2 and pathogenic variants in the <i>SALL1</i>, <i>RECQL4</i>, <i>NF1</i>, <i>CASK,</i> and <i>PAH</i> genes. These observations indicated that integrated cytogenetic and genomic analyses should be offered to patients with phenotypic abnormalities outside the spectrum of the T8M syndrome for comprehensive laboratory diagnosis and clinical management.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"4494577"},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12855162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107582","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}

{"title":"Hypokalemic Periodic Paralysis Associated With a Rare <i>CACNA1S</i> Variant (p.Leu1243Val): Expanding the Mutational Spectrum.","authors":"Mark Abi Nader","doi":"10.1155/crig/8824228","DOIUrl":"10.1155/crig/8824228","url":null,"abstract":"<p><strong>Background: </strong>Hypokalemic periodic paralysis (HypoPP) is a rare skeletal muscle channelopathy, most often caused by mutations in <i>CACNA1S</i> or <i>SCN4A</i>. Most pathogenic <i>CACNA1S</i> mutations affect arginine residues in S4 voltage-sensor domains, but other variants remain poorly understood.</p><p><strong>Case presentation: </strong>I describe a 30-year-old Caucasian woman with recurrent paralytic episodes and hypokalemia (2.1-2.3 mmol/L), triggered by stress and carbohydrate-rich meals. Genetic testing revealed heterozygosity for <i>CACNA1S</i> c.3727C  >  G (p.Leu1243Val), a variant of uncertain significance not previously associated with pathogenicity. Her phenotype was consistent with HypoPP. Treatment with spironolactone and acetazolamide reduced episode frequency, although the latter caused intolerable side effects, particularly tachypnea; she was later approved for dichlorphenamide. During one hospitalization, she also developed transient hypophosphatemia and hypokalemia, consistent with her HypoPP picture. Kidney function and imaging were normal. Family history revealed electrolyte disturbances in her grandfather.</p><p><strong>Conclusions: </strong>This case highlights a possible genotype-phenotype link involving <i>CACNA1S</i> p.Leu1243Val. Continued reporting of such cases is essential for variant reclassification and for improving recognition of metabolic shifts during HypoPP attacks.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"8824228"},"PeriodicalIF":0.0,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12808331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999244","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}

{"title":"Phenotypic Spectrum of Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) in Denmark: A Case Series Characterizing the First Danish Families With the <i>APC</i> Promotor 1B Variant c.-191T > C.","authors":"P A Skat-Rørdam, A M Jelsig, J G Karstensen, A H Petersen, M B Madsen, T D Jensen","doi":"10.1155/crig/4024148","DOIUrl":"10.1155/crig/4024148","url":null,"abstract":"<p><p>Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare autosomal dominantly inherited gastric cancer syndrome that is characterized by fundic gland polyposis of the stomach (> 100) and an increased risk of gastric cancer. The genetic cause is recognized as a pathogenic variant in the promotor 1B of the APC gene. Presently, there are no established clinical criteria, and current guidelines are based on limited evidence. In this report, we identified two families with GAPPS. Family I had a family history of gastric cancer, and we identified seven family members with GAPPS. The diagnosis was verified by endoscopic findings of polyposis and genetic analysis identifying a variant in the promotor 1B of the APC gene, NM_001127511.3: c.-191T > C. In Family II, the same pathogenic variant, NM_001127511.3: c.-191T > C, was detected as an incidental finding in a 61-year-old patient with hepatocellular carcinoma, clear cell renal carcinoma, and small cell lung cancer. An esophagogastroduodenoscopy (EGD) at the age of 59 had revealed only one small fundic polyp. This is the first report of patients with GAPPS from Denmark, and it emphasizes the variable phenotypic expression and subsequently the difficulty of surveillance and genetic counseling in these patients and their families.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"4024148"},"PeriodicalIF":0.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953227","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}

{"title":"Identification of a Novel <i>DNAAF3</i> Variant in a 54-Year-Old Patient With Newly Diagnosed Primary Ciliary Dyskinesia (PCD).","authors":"Mirja M Wirtz, Sabine Ebner, Anna Pleyers, Natalie Firlei-Fleischmann, Richard Untersteiner, Michael Studnicka","doi":"10.1155/crig/5137651","DOIUrl":"10.1155/crig/5137651","url":null,"abstract":"<p><p>Primary ciliary dyskinesia (PCD) is a rare and heterogeneous inherited disease characterized by impaired mucociliary clearance. Patients with PCD typically present with recurrent respiratory infections resulting in the development of bronchiectasis. Even though awareness of the disease has increased over the years, PCD remains underdiagnosed. We here present a case of a newly diagnosed middle-aged female found to have a previously undescribed variant of the disease-associated <i>DNAAF3</i> gene.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"5137651"},"PeriodicalIF":0.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12775340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145935521","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}

{"title":"Correction to \"Intellectual Disability and Blended Phenotypes: Insights from a Centre in North India\".","authors":"","doi":"10.1155/crig/9761675","DOIUrl":"10.1155/crig/9761675","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1155/2024/6009569.].</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2025 ","pages":"9761675"},"PeriodicalIF":0.0,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890403","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}