BMC Medical Genomics最新文献

{"title":"Hypercalcemia and co-occurring TBX1 mutation in Glycogen Storage Disease Type Ib: case report.","authors":"Zakaria Kasmi, Imane Ain El Hayat, Zahra Aadam, Abderrahmane Errami, Ibtihal Benhsaien, Jalila El Bakkouri, Dalal Ben Sabbahia, Meryem Atrassi, Ahmed Aziz Bousfiha, Fatima Ailal","doi":"10.1186/s12920-024-02057-5","DOIUrl":"10.1186/s12920-024-02057-5","url":null,"abstract":"<p><p>Glycogen Storage Disease Type Ib (GSD-Ib) is a rare autosomal recessive metabolic disorder caused by mutations in SLC37A4, leading to a deficiency in glucose-6-phosphate translocase. This disorder is characterized by impaired glycogenolysis and gluconeogenesis, resulting in clinical and metabolic manifestations. We report a three-month-old Moroccan female patient presenting with doll-like facies, hepatomegaly, dysmorphic features, and developmental delays. Laboratory analysis revealed hypoglycemia, elevated triglyceride levels, hypercalcemia, and neutropenia. Genetic testing confirmed a homozygous pathogenic variant in SLC37A4 and a heterozygous variant of uncertain significance in TBX1. Initial management included a lactose-free and galactose-free diet, multivitamin supplementation, and granulocyte colony-stimulating factor (G-CSF) therapy to address neutropenia. A novel aspect of this case involves hypercalcemia as an unusual finding in GSD-Ib and the co-occurrence of a variant in the TBX1 gene, which is not typically associated with the disease but may contribute to the patient's clinical presentation. These findings add a new dimension to our understanding of GSD-Ib and suggest potential avenues for future research to elucidate these genetic interactions and their impact on clinical outcomes.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"5"},"PeriodicalIF":2.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055780","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}

{"title":"Discovering the interactome, functions, and clinical relevance of enhancer RNAs in kidney renal clear cell carcinoma.","authors":"Zhaohui Sun, Haojie Du, Xudong Zheng, Hepeng Zhang, Huajie Hu","doi":"10.1186/s12920-024-02081-5","DOIUrl":"https://doi.org/10.1186/s12920-024-02081-5","url":null,"abstract":"<p><p>Enhancer RNA (eRNA) has emerged as a key player in cancer biology, influencing various aspects of tumor development and progression. In this study, we investigated the role of eRNAs in kidney renal clear cell carcinoma (KIRC), the most common subtype of renal cell carcinoma. Leveraging high-throughput sequencing data and bioinformatics analysis, we identified differentially expressed eRNAs in KIRC and constructed eRNA-centric regulatory networks. Our findings revealed that up-regulated eRNAs in KIRC potentially regulate immune response and hypoxia pathways, while down-regulated eRNAs may impact ion transport, cell cycle, and metabolism. Furthermore, we developed a diagnostic prediction model based on eRNA expression profiles, demonstrating its effectiveness in KIRC diagnosis. Finally, we elucidated the regulatory mechanism of an eRNA (ENSR00000305834) on the expression of SLC15A2, a potential prognostic biomarker in KIRC, through bioinformatics analysis and in vitro validation experiments. In summary, Our study highlights the clinical significance of eRNAs in KIRC and underscores their potential as therapeutic targets.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"3"},"PeriodicalIF":2.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926369","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}

{"title":"Integrative analyses of mendelian randomization and bioinformatics reveal casual relationship and genetic links between COVID-19 and knee osteoarthritis.","authors":"Xiao Zheng, Jinhao Li, Qinfeng Ma, Jianping Gong, Jianbo Pan","doi":"10.1186/s12920-024-02074-4","DOIUrl":"10.1186/s12920-024-02074-4","url":null,"abstract":"<p><strong>Background: </strong>Clinical and epidemiological analyses have found an association between coronavirus disease 2019 (COVID-19) and knee osteoarthritis (KOA). Infection with COVID-19 may increase the risk of developing KOA.</p><p><strong>Objectives: </strong>This study aimed to investigate the potential causal relationship between COVID-19 and KOA using Mendelian randomization (MR) and to explore the underlying mechanisms through a systematic bioinformatics approach.</p><p><strong>Methods: </strong>Our investigation focused on exploring the potential causal relationship between COVID-19, acute upper respiratory tract infection (URTI) and KOA utilizing a bidirectional MR approach. Additionally, we conducted differential gene expression analysis using public datasets related to these three conditions. Subsequent analyses, including transcriptional regulation analysis, immune cell infiltration analysis, single-cell analysis, and druggability evaluation, were performed to explore potential mechanisms and prioritize therapeutic targets.</p><p><strong>Results: </strong>The results indicate that COVID-19 has a one-way impact on KOA, while URTI does not play a causal role in this association. Ribosomal dysfunction may serve as an intermediate factor connecting COVID-19 with KOA. Specifically, COVID-19 has the potential to influence the metabolic processes of the extracellular matrix, potentially impacting the joint homeostasis. A specific group of genes (COL10A1, BGN, COL3A1, COMP, ACAN, THBS2, COL5A1, COL16A1, COL5A2) has been identified as a shared transcriptomic signature in response to KOA with COVID-19. Imatinib, Adiponectin, Myricetin, Tranexamic acid, and Chenodeoxycholic acid are potential drugs for the treatment of KOA patients with COVID-19.</p><p><strong>Conclusions: </strong>This study uniquely combines Mendelian randomization and bioinformatics tools to explore the possibility of a causal relationship and genetic association between COVID-19 and KOA. These findings are expected to provide novel perspectives on the underlying biological mechanisms that link COVID-19 and KOA.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"2"},"PeriodicalIF":2.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920611","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}

{"title":"Bioinformatics analysis of miR-2861 and miR-5011-5p that function as potential tumor suppressors in colorectal carcinogenesis.","authors":"Alper Aytekin, Hikmet Kadakal, Deniz Mihcioglu, Turkan Gurer","doi":"10.1186/s12920-024-02080-6","DOIUrl":"10.1186/s12920-024-02080-6","url":null,"abstract":"<p><strong>Background: </strong>The study aimed to was to investigate the relationship between miR-2861, miR-5011-5p, and colorectal carcinogenesis.</p><p><strong>Method: </strong>In the present study, it was isolated RNA from both the tumor and non-tumor tissue of a total of 80 CRC patients and after synthesizing the cDNA, it was performed qRT-PCR to determine the expression levels of miR‑2861 and miR‑5011-5p. In addition, it was predicted that dysregulated miRNAs targets, pathways and functional gene annotations that may be important in colorectal carcinogenesis using KEGG pathway and GO analysis.</p><p><strong>Results: </strong>The resulting data revealed that both expression levels of miR-2861 and miR-5011-5p were significantly decreased in tumor tissues compared with non-tumor tissues of CRC patients. The GO and KEGG pathway analysis showed that miR-2861 and miR-5011-5p may participate in multiple the biological process, cellular components, and molecular function subcategories such as mitotic cell cycle, regulation of small GTPase mediated signal transduction, cell death, and acid binding transcription factor activity. It was also revealed that target genes of miRNAs can be found in signaling pathways such as TGF-beta, Rap1, Ras, cAMP, Wnt, mTOR and, PI3K-Akt signaling pathways.</p><p><strong>Conclusion: </strong>These findings imply that miR-2861 and miR-5011-5p might function as tumor suppressors in the development of CRC.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920607","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}

{"title":"Genetic analysis of partial duplication of the long arm of chromosome 16.","authors":"Dan Tang, Ai Chen, Jing Xu, Yu Huang, Jun Fan, Jin Wang, Hui Zhu, Guanghuan Pi, Li Yang, Fu Xiong, Zemin Luo, Gen Li, Lan Zeng, Shuyao Zhu","doi":"10.1186/s12920-024-02059-3","DOIUrl":"10.1186/s12920-024-02059-3","url":null,"abstract":"<p><strong>Background: </strong>Pure partial trisomy 16q12.1q22.1 is a rare chromosome copy number variant (CNV). The primary clinical phenotypes associated with this syndrome include abnormal facial morphology, global developmental delay (GDD), short stature, and reported predisposing factors for atypical behavior, autism, the development of learning disabilities, and neuropsychiatric disorders. The dosage-sensitive genes associated with partial trisomy are not disclosed preventing to establish a genotype-phenotype correlation.</p><p><strong>Methods: </strong>We report a case of a Chinese patient diagnosed with GDD and an abnormal facial shape, who was found to have partial trisomy 16 through karyotyping and high-throughput sequencing analysis. Karyotype and CNV tracing analyses were also conducted on the biological parents of the patient to assess for any chromosomal structural abnormalities. Additionally, we included 29 patients with pure partial trisomy 16q, reported in the DECIPHER database and the literature. We and performed a genotype-phenotype correlation analysis.</p><p><strong>Results: </strong>The proband, a 2-year-old female, was found to have a de novo 21.96 Mb duplication located between 16q12.1q22.1, with no other deletions observed on other chromosomes, indicating a pure partial trisomy of 16q. Through genotype and phenotype analysis of 29 individuals, we found that patients with the duplicated region located at the distal region of 16q may exhibit more severe symptoms than those with duplication at the proximal region; however, no relationship was identified between phenotype and the size of the duplicated segment.</p><p><strong>Conclusion: </strong>We report, for the first time, a patient with partial trisomy 16q validated by multiple genetic tests, including CNV-seq, whole exome sequencing (WES), and karyotyping. It is speculated that partial trisomy of 16q may be associated with continuous gene duplication. However, functional studies are necessary to identify the causative gene or critical region linked to duplication syndrome of chromosome 16q.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"294"},"PeriodicalIF":2.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881153","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}

{"title":"Effects of different temperatures on chondrocyte growth: a transcriptomic analysis.","authors":"Wei Zhao, Yingsong Wang, Jingming Xie, Jin Zhou, Zhi Zhao, Tao Li, Zhiyue Shi, Jie Xiao","doi":"10.1186/s12920-024-02070-8","DOIUrl":"10.1186/s12920-024-02070-8","url":null,"abstract":"<p><strong>Background: </strong>Our previous study demonstrated that temperature-related microwave ablation (MWA) can safely modulate growth plates of piglets' vertebrae. Therefore, this study is designed to investigate the effects of different temperatures on chondrocyte viability and the underlying molecular mechanisms in vitro.</p><p><strong>Methods: </strong>Following a 10-minute treatment at different temperatures (37 °C, 40 °C, 42 °C, 44 °C, 46 °C, 48 °C, and 50 °C), CCK-8 assay was used to examine the viability of ATDC5 cells at 12 h. Differentially expressed genes (DEGs) and the hub genes in ATDC5 cells treated at 37 °C, 40 °C and 44 °C were identified using RNA-seq. The expression of hub genes in ATDC5 cells was validated using RT-qPCR.</p><p><strong>Results: </strong>Compared with 37 °C, exposure to 40 °C significantly increased the viability of ATDC5 cells, while 42 °C had no significant effect. Additionally, exposure to 44 °C, 46 °C, 48 °C, and 50 °C exhibited the opposite pattern, with ATDC5 cells being particularly less than 50% active after treatment at 46 °C, 48 °C, and 50 °C. Differential expression analysis identified 179, 374 and 221 DEGs in the comparisons of 40 °C vs. 37 °C, 44 °C vs. 37 °C, and 44 °C vs. 40 °C, respectively. These DEGs predominantly regulated proliferation, differentiation, necrosis, inflammatory and immune responses, and ECM synthesis/degradation. Furthermore, they were associated with the Ras, PI3K/AKT, mTOR, cAMP, and MAPK pathways. Agt, Hspa1a, Hspb1, and Nlrc4 were identified as hub genes in DEGs, and RT-qPCR confirmed that the mRNA expression patterns of these hub genes in ATDC5 cells were largely consistent with the RNA-seq results.</p><p><strong>Conclusion: </strong>The regulation of chondrocyte viability by temperature is associated with Ras, PI3K/AKT, mTOR, cAMP, and MAPK pathways. Additionally, Agt, Hspa1a, Hspb1, and Nlrc4 may be the key regulatory genes in this process.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"293"},"PeriodicalIF":2.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871209","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}

{"title":"Clinical characteristics and genetic analysis of four pediatric patients with Kleefstra syndrome.","authors":"Rong Ren, Yedan Liu, Peipei Liu, Jing Zhao, Mei Hou, Shuo Li, Zongbo Chen, Aiyun Yuan","doi":"10.1186/s12920-024-02065-5","DOIUrl":"10.1186/s12920-024-02065-5","url":null,"abstract":"<p><strong>Background: </strong>Kleefstra syndrome spectrum (KLEFS) is an autosomal dominant disorder that can lead to intellectual disability and autism spectrum disorders. KLEFS encompasses Kleefstra syndrome-1 (KLEFS1) and Kleefstra syndrome-2 (KLEFS2), with KLEFS1 accounting for more than 75%. However, limited information is available regarding KLEFS2. KLEFS1 is caused by a subtelomeric chromosomal abnormality resulting in either deletion at the end of the long arm of chromosome 9, which contains the EHMT1 gene, or by variants in the EHMT1 gene and the KMT2C gene that cause KLEFS2.</p><p><strong>Methods: </strong>This study was a retrospective analysis of clinical data from four patients with KLEFS. Exome sequencing (ES) and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of genotype‒phenotype correlations of the EHMT1 and KMT2C genes. Protein structure modeling was performed to evaluate the effects of the variants on the protein's three-dimensional structure. In addition, real-time quantitative reverse transcription‒polymerase chain reaction (RT‒qPCR) and western blotting were used to examine the protein and mRNA levels of the KMT2C gene.</p><p><strong>Results: </strong>Two patients with KLEFS1 were identified: one with a novel variant (c.2382 + 1G > T) and the other with a previously reported variant (c.2426 C > T, p.Pro809Leu) in the EHMT1 gene. A De novo deletion at the end of the long arm of chromosome 9 was also reported. Furthermore, a patient with KLEFS2 was identified with a novel variant in the KMT2C gene (c.568 C > T, p.Arg190Ter). The RT‒qPCR and western blot results revealed that the expression of the KMT2C gene was downregulated in the KLEFS2 sample.</p><p><strong>Conclusion: </strong>This study contributes to the understanding of both KLEFS1 and KLEFS2 by identifying novel variants in EHMT1 and KMT2C genes, thereby expanding the variant spectrum. Additionally, we provide the first evidence of how a KMT2C variant leads to decreased gene and protein expression, enhancing our understanding of the molecular mechanisms underlying KLEFS2. Based on these findings, children exhibiting developmental delay, hypotonia, distinctive facial features, and other neurodevelopmental abnormalities should be considered for ES to ensure early intervention and treatment.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"290"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852128","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}

{"title":"Associations between (pharmaco-)genetic markers and postoperative pain after inguinal hernia repair - a prospective study protocol.","authors":"Florine M Wiss, Ulrich Dietz, Andreas Thalheimer, Sebastian Lamm, Robert Rosenberg, Samuel S Allemann, Henriette E Meyer Zu Schwabedissen, Anna Bollinger, Markus L Lampert","doi":"10.1186/s12920-024-02064-6","DOIUrl":"10.1186/s12920-024-02064-6","url":null,"abstract":"<p><strong>Background: </strong>Postoperative pain is a common complication following surgery, with severity and duration varying between patients. Chronic postoperative pain after inguinal hernia surgery has an incidence rate of approximately 10%. Risk factors for acute and chronic pain following hernia surgery include age, sex, psychosocial factors, and demographic background. Additionally, genetic polymorphisms in enzymes involved in pain mechanisms, as well as the metabolism of analgesics might influence pain perception, pain development, and response to pain medications. Key enzymes include the catechol-o-methyltransferase (COMT), the µ-opioid receptor 1 (OPRM1), and the cytochrome P450 2D6 (CYP2D6). CYP2D6 plays a crucial role in metabolizing analgesics such as tramadol, codeine, and oxycodone. It is also suspected to be involved in the synthesis of catecholamines and endogenous morphines suggesting a potential role in pathophysiology of pain. We hypothesize that the CYP2D6 activity influences the development of postoperative pain after hernia surgery.</p><p><strong>Methods: </strong>This study is a prospective, observational, multicenter association study investigating adult patients scheduled for inguinal hernia surgery using a robotic-assisted (rTAPP) approach. Patients are enrolled during the preoperative surgical consultation. A buccal swab is collected for genetic testing at this time. Pain at the site of the hernia is assessed using the validated EuraHSQoL score preoperatively and at 2, 4, and 6 weeks postoperatively. Additionally, information on co-medication and details of the surgery will be collected. The planned number of participants is 350 patients. The primary objective is to analyze the association between different genotype-predicted CYP2D6 phenotypes and patient-reported pain intensity 6 weeks after surgery. Secondary objectives include the association between further genetic variants, such as the COMT rs4680 and OPRM1 rs1799971 genotype, and pain severity. Additionally, the potential of pharmacogenetic panel testing to optimize analgesic therapy in hernia surgery patients will be explored.</p><p><strong>Discussion: </strong>The findings of this study are expected to provide valuable insights into identifying patients at higher risk for postoperative pain before surgery. This knowledge could pave the way for tailored interventions during and after surgery for these specific patients.</p><p><strong>Trial registration: </strong>Deutsches Register Klinischer Studien https://www.drks.de/DRKS00034796 Registered on August 07, 2024.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"286"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852121","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}

{"title":"Prenatal diagnosis and molecular cytogenetic analysis of pure chromosome 10p15.3 microdeletion using chromosomal microarray analysis.","authors":"Na Zhang, Nan Huang, Yu'e Chen, Xinying Chen, Jianlong Zhuang","doi":"10.1186/s12920-024-02063-7","DOIUrl":"10.1186/s12920-024-02063-7","url":null,"abstract":"<p><strong>Background: </strong>The literature contains exceedingly limited reports on chromosome 10p15.3 microdeletions. In the present study, two cases of fetuses with pure terminal 10p15.3 microdeletion syndrome in a Chinese population were examined, with the objective of enhancing understanding of the genotype-phenotype correlation associated with 10p15.3 microdeletions.</p><p><strong>Methods: </strong>Two fetuses with chromosome 10p15.3 microdeletion were identified from a cohort of 5,258 cases undergoing amniocentesis. Karyotyping and chromosomal microarray analysis (CMA) was conducted to assess chromosomal abnormalities and detect copy number variations (CNVs) within the families, respectively.</p><p><strong>Results: </strong>In Family 1, the fetus exhibited a 556.2-Kb deletion in the 10p15.3 region, encompassing OMIM genes such as DIP2C and ZMYND11, and presented with increased nuchal translucency on prenatal ultrasound examination. Parental CMA analysis revealed that the 10p15.3 microdeletion was inherited from the father, who displayed mild language impairment. In Family 2, a comparable 10p15.3 microdeletion was identified in a fetus presenting with asymmetric butterfly vertebrae at T10 and T12, along with mild scoliosis of the spine. Family 1 elected to terminate the pregnancy, while Family 2 chose to continue. At a follow-up conducted at one year and eight months, the child demonstrated delays in both speech and motor development.</p><p><strong>Conclusion: </strong>The present study is the first to report two cases of pure terminal chromosome 10p15.3 microdeletion syndrome in fetuses, offering valuable insights for the prenatal diagnosis of 10p15.3 microdeletion syndrome. Further, it is the first to describe mild clinical features, specifically limited to language impairment, in a patient with 10p15.3 microdeletion syndrome.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"287"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852149","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}

{"title":"Novel pathogenic variant in a mild case of type B molybdenum cofactor deficiency: case report and literature review.","authors":"Morgan Kinsinger, Jelena Ivanisevic, Divakar S Mithal","doi":"10.1186/s12920-024-02027-x","DOIUrl":"10.1186/s12920-024-02027-x","url":null,"abstract":"<p><strong>Background: </strong>Molybdenum cofactor deficiency (MoCD) is a rare metabolic disorder caused by pathogenic variants in the highly conserved biosynthetic pathway of molybdenum cofactor (MoCo), resulting in sulfite intoxication. MoCD may present in a clinically severe, fatal form marked by intractable seizures after birth, hyperekplexia, microcephaly and cerebral atrophy, or a later onset form with a more varied clinical course. Three types of MoCD have been described based on the effected gene along the MoCo synthesis pathway: type A (MOCS1); type B (MOCS2 or MOCS3) and type C (GPHN). The MOCS2 gene is bicistronic, encoding the small (MOCS2A) and large (MOCS2B) subunits with an overlapping coding region. This case report describes a patient with the first known variant causative of mild disease in the overlapping bicistronic region (c.263 G > C) and the first ever described in the highly conserved C-terminal glycine-glycine motif of MOCS2A.</p><p><strong>Case presentation: </strong>The patient developed normally until age 12 months when she presented in the setting of acute illness with developmental regression, low serum uric acid, and MRI with bilateral globus pallidus (GP) injury. Exome sequencing identified a homozygous variant of unknown significance in the MOCS2 gene and the diagnosis of MoCD type B was confirmed by the patient's low serum uric acid coupled with elevated urine sulfocysteine and associated metabolites, resulting in gene reclassification. Nearly four years after her initial presentation she has demonstrated progress in language and motor domains, consistent with a mild phenotype of MoCD.</p><p><strong>Conclusions: </strong>The case emphasizes challenges in identifying atypical forms of rare diseases, the importance of exome sequencing to identify mild cases of MoCD, and the ongoing challenges with understanding the MOCS2 gene. While one FDA approved treatment exists for MoCD type A, further research into the mechanisms of phenotype-genotype differences among this patient population may aid in additional therapeutic options for MoCD.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"292"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852087","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}