Molecular Genetics & Genomic Medicine最新文献

{"title":"Identification of two novel heterozygous variants of SMC3 with Cornelia de Lange syndrome.","authors":"Zhi Lei, Xiaorui Song, Xuan Zheng, Yanhong Wang, Yingyuan Wang, Zhirong Wu, Tian Fan, Shijie Dong, Honghui Cao, Yuefang Zhao, Zhiyi Xia, Liujiong Gao, Qing Shang, Shiyue Mei","doi":"10.1002/mgg3.2447","DOIUrl":"10.1002/mgg3.2447","url":null,"abstract":"<p><strong>Background: </strong>Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder, and cases caused by variants in the structural maintenance of chromosomes protein 3 (SMC3) gene are uncommon. Here, we report two cases of CdLS associated with novel pathogenic variants in SMC3 from two Chinese families.</p><p><strong>Methods: </strong>Clinical presentations of two patients with CdLS were evaluated, and specimens from the patients and other family members were collected for Trio-based whole-exome sequencing. Pyrosequencing, chip-based digital PCR, minigene splicing assay, and in silico analysis were carried out to elucidate the impact of novel variants.</p><p><strong>Results: </strong>Novel heterozygous variants in SMC3 were identified in each proband. One harbored a novel splicing and mosaic variant (c.2535+1G>A) in SMC3. The mutated allele G>A conversion was approximately 23.1% by digital PCR, which indicated that 46.2% of peripheral blood cells had this variant. Additionally, in vitro minigene splicing analysis validated that the c.2535+1G>A variant led to an exon skipping in messenger RNA splicing. The other carried a heterozygous variant (c.435C>A), which was predicted to be pathogenic as well as significantly altered in local electrical potential. The former showed multiple abnormalities and marked clinical severity, and the latter mainly exhibited a speech developmental disorder and slightly facial anomalies.</p><p><strong>Conclusion: </strong>Both patients were clinically diagnosed with Cornelia de Lange syndrome 3 (CdLS3). The newly identified SMC3 gene variants can expand the understanding of CdLS3 and provide reliable evidence for genetic counseling to the affected family.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909605","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":"Mexican patient with Ellis-van Creveld syndrome and cleft palate: Importance of functional hemizygosity and phenotype expansion.","authors":"Luis Felipe León-Madero, Cesar Humberto Fregoso-Ron, Juan Carlos De León-Carbajal, Juan Manuel Valdés-Miranda","doi":"10.1002/mgg3.2451","DOIUrl":"10.1002/mgg3.2451","url":null,"abstract":"<p><strong>Background: </strong>Ellis-van Creveld syndrome (EvCS) is a chondroectodermal dysplasia caused by germline pathogenic variants in ciliary complex subunit 1 and 2 genes (EVC, EVC2) on chromosome 4p16.2. This disease has a broad phenotype, and there are few described phenotype-genotype correlations.</p><p><strong>Methods: </strong>Ethical Compliance: Written informed consent was obtained from the parents. Here, we report a genetically confirmed Mexican patient with EvCS having two inherited pathogenic variants in trans in EVC2: c.[1195C>T];[2161delC].</p><p><strong>Results: </strong>This patient allowed a genotypic-phenotypic comparison with another Mexican subject who presented a more attenuated phenotype; furthermore, our patient also presented cleft palate, a rarely reported feature.</p><p><strong>Conclusion: </strong>Our case shows the importance of comparing functional hemizygosity between patient's phenotypes when they share a variant, and our case also supports the association of alterations in the palate as part of the EvCS phenotype.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958386","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":"A new genetic diagnosis strategy for paroxysmal kinesigenic dyskinesia: Targeted high-throughput detection of PRRT2 gene c.649 locus.","authors":"Min Wen, Hui Huang, Fei Huang, Ru Xu, Jing Zhang, Jia-Geng Fan, Jun Zeng, Kai-Wen Jiang, Ding Liu, Hua-Lin Huang, Qing-Nan He","doi":"10.1002/mgg3.2469","DOIUrl":"10.1002/mgg3.2469","url":null,"abstract":"<p><strong>Background: </strong>Paroxysmal kinesigenic dyskinesia (PKD) is the most prevalent kind type of paroxysmal Dyskinesia, characterized by recurrent and transient episodes of involuntary movements. Most PKD cases were attributed to the proline-rich transmembrane protein 2 (PRRT2) gene, in which the c.649 region is a hotspot for known mutations. Even though some patients with PKD have been genetically diagnosed using whole-exome sequencing (WES) and Sanger sequencing, there are still cases of missed diagnoses due to the limitations of sequencing technology and analytic methods on throughput.</p><p><strong>Methods: </strong>Patients meeting the diagnosis criteria of PKD with negative results of PRRT2-Sanger sequencing and WES were included in this study. Mutation screening and targeted high-throughput sequencing were performed to analyze and verify the sequencing results of the potential mutations.</p><p><strong>Results: </strong>Six patients with PKD with high mutation ratios of c.649dupC were screened using our targeted high-throughput sequencing from 26 PKD patients with negative results of PRRT2-Sanger sequencing and WES (frequency = 23.1%), which compensated for the comparatively shallow sequencing depth and statistical flaws in this region. Compared with the local normal population and other patients with PKD, the mutation ratios of c.649dupC of these six patients with PKD were much higher and also had truncated protein structures and differentially altered mRNA expression.</p><p><strong>Conclusion: </strong>Based on the above studies, we emphasize the routine targeted high-throughput sequencing of the c.649 site in the PRRT2 gene in so-called genetic-testing-negative patients with PKD, and manually calculate the deletion and duplication mutations depth and ratios to lower the rate of clinical misdiagnosis.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11112295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080403","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":"Short report: Twins with 20p13 duplication. Case report and comprehensive literature review.","authors":"Benjamin J Kennedy, Sarah K Savage, Stephen G Kaler","doi":"10.1002/mgg3.2436","DOIUrl":"10.1002/mgg3.2436","url":null,"abstract":"<p><strong>Background: </strong>Trisomy 20p is a rare genetic condition caused by a duplication of the short arm of chromosome 20.</p><p><strong>Methods: </strong>We employed clinical observation and molecular genetic testing (SNP microarray), to study identical twin males with an unknown dysmorphic syndrome. We conducted a literature review of trisomy 20p and collated the clinical and molecular genetic findings on 20 affected subjects reported since 2000.</p><p><strong>Results: </strong>Identical twin males, whose prenatal course was complicated by a twin-to-twin transfusion, manifested profound language and neurocognitive delays as well as distinctive facial dysmorphisms when evaluated at 2 years of age. SNP microarray identified identical duplications of 20p13 with no other chromosomal aberrations. A literature survey of 20p trisomy syndrome identified 20 other examples of this condition reported since 2000, which we collated with 33 summarized by Sidwell et al. (2000). Within the combined total of 55 affected individuals, we found a distinctive clinical phenotype that provides insight on the effects of abnormal dosage of genes in 20p13. These loci include FAM110A (OMIM 611393), ANGPT4 (OMIM 603705), RSPO4 (OMIM 610573), PSMF1 (OMIM 617858), SNPH (OMIM 604942), SDCBP2 (OMIM 617358), FKBP1A (OMIM 186945), TMEM74B, C20orf202, and RAD21L1 (OMIM 619533). Gene profiling highlighted that syntaphilin (SNPH) is highly expressed in mammalian brain, where it is considered critical for mitochondrial transport in neuronal axons, and to directly influence axonal morphogenesis and function.</p><p><strong>Conclusion: </strong>We propose that abnormal activity of syntaphilin engendered by the trisomy is primarily responsible for the language, neurocognitive, and gross motor delays reported in individuals with 20p trisomy. Additional studies, for example, characterization of cerebral organoids generated from affected patients may help to better understand this condition, and potentially suggest rational remedies to improve the lives of affected individuals and their families.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912562","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":"Diagnosis of Arboleda-Tham syndrome by whole-exome sequencing in an Asian girl with severe developmental delay.","authors":"Qingran Wang, Yujiao Zhang, Li Li, Ning Yang","doi":"10.1002/mgg3.2420","DOIUrl":"10.1002/mgg3.2420","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to report a severe phenotype of Arboleda-Tham syndrome in a 20-month-old girl, characterized by global developmental delay, distinct facial features, intellectual disability. Arboleda-Tham syndrome is known for its wide phenotypic spectrum and is associated with truncating variants in the KAT6A gene.</p><p><strong>Methods: </strong>To diagnose this case, a combination of clinical phenotype assessment and whole-exome sequencing technology was employed. The genetic analysis involved whole-exome sequencing, followed by confirmation of the identified variant through Sanger sequencing.</p><p><strong>Results: </strong>The whole-exome sequencing revealed a novel de novo frameshift mutation c.3048del (p.Leu1017Serfs*17) in the KAT6A gene, which is classified as likely pathogenic. This mutation was not found in the ClinVar and HGMD databases and was not present in her parents. The mutation leads to protein truncation or activation of nonsense-mediated mRNA degradation. The mutation is located within exon 16, potentially leading to protein truncation or activation of nonsense-mediated mRNA degradation. Protein modeling suggested that the de novo KAT6A mutation might alter hydrogen bonding and reduce protein stability, potentially damaging the protein structure and function.</p><p><strong>Conclusion: </strong>This study expands the understanding of the genetic basis of Arboleda-Tham syndrome, highlighting the importance of whole-exome sequencing in diagnosing cases with varied clinical presentations. The discovery of the novel KAT6A mutation adds to the spectrum of known pathogenic variants and underscores the significance of this gene in the syndrome's pathology.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11109524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076208","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":"Identification and functional analysis of a rare variant of gene DHX37 in a patient with 46,XY disorders of sex development.","authors":"Wei Jiang, Jing Yu, Yu Mao, Yunman Tang, Li Cao, Qin Du, Jianan Li, Jiyun Yang","doi":"10.1002/mgg3.2453","DOIUrl":"10.1002/mgg3.2453","url":null,"abstract":"<p><strong>Background: </strong>46,XY sex reversal 11 (SRXY11) [OMIM#273250] is characterized by genital ambiguity that may range from mild male genital defects to gonadal sex reversal in severe cases. DHX37 is an RNA helicase that has recently been reported as a cause of SRXY11. So far, a total of 21 variants in DHX37 have been reported in 58 cases with 46,XY disorders of sex development (DSD).</p><p><strong>Methods: </strong>Whole exome sequencing (WES) was conducted to screen for variations in patients with 46,XY DSD. The subcellular localization of mutant DHX37 proteins was detected by immunofluorescence. And the levels of mutant DHX37 proteins were detected via Western blotting.</p><p><strong>Results: </strong>A novel pathogenic variant of DHX37 was identified in a patient with 46,XY DSD c.2012G > C (p.Arg671Thr). Bioinformatics analysis showed that the protein function of the variant was impaired. Compared with the structure of the wild-type DHX37 protein, the number of hydrogen bonds and interacting amino acids of the variant protein were changed to varying degrees. In vitro assays revealed that the variant had no significant effect on the intracellular localization of the protein but significantly reduced the expression level of the protein.</p><p><strong>Conclusions: </strong>Our finding further expands the spectrum of the DHX37 variant and could assist in the molecular diagnosis of 46,XY DSD patients.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11106588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071504","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":"Osteomesopyknosis associated with a novel ALOX5 variant that impacts the RANKL pathway.","authors":"Jose L Fernandez-Luna, José L Hernández, Soraya Curiel-Olmo, Néstor A Martínez-Amador, Ana I Vega, Remedios Quirce, Santiago Montes-Moreno, Olga Gutierrez, Alvaro Del Real, Carolina Sañudo, Jose A Riancho","doi":"10.1002/mgg3.2471","DOIUrl":"10.1002/mgg3.2471","url":null,"abstract":"<p><strong>Background: </strong>Bone tissue homeostasis relies on the coordinated activity of the bone-forming osteoblasts and bone-resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown.</p><p><strong>Methods: </strong>We present a case report encompassing clinical assessments, imaging studies, and whole-exome sequencing analysis, complemented by functional in vitro experiments.</p><p><strong>Results: </strong>This new case of osteomesopyknosis was associated with a missense ALOX5 variant predicted to induce protein misfolding and proteasomal degradation. Transfection experiments demonstrated that the variant was associated with reduced protein levels restored by proteasomal inhibition with bortezomib. Likewise, gene expression analysis showed that the mutated gene was associated with a decreased RANKL/OPG ratio, which is a critical driver of osteoclast precursor differentiation.</p><p><strong>Conclusion: </strong>Our data indicate impaired bone resorption as the underlying mechanism of this rare osteosclerosis, implicating ALOX5 pathogenic variants as potential etiological factors.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11130582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158295","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":"Association of a genetic variant in angiopoietin‐like 3 with serum HDL‐C and risk of cardiovascular disease: A study of the MASHAD cohort over 6 years","authors":"Malihe Aghasizadeh, Asieh Ahmadi Hoseini, Reza Sahebi, Tooba Kazemi, Parisa Asadiyan‐Sohan, Habibollah Esmaily, Sara Samadi, Amir Avan, Gordon A. Ferns, Saeede Khosravi, Hamideh Ghazizadeh, Ebrahim Miri‐Moghaddam, Majid Ghayour‐Mobarhan","doi":"10.1002/mgg3.2418","DOIUrl":"https://doi.org/10.1002/mgg3.2418","url":null,"abstract":"BackgroundLoss‐of‐function (LOF) variants of the angiopoietin‐like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high‐density lipoprotein cholesterol (HDL‐C) concentrations and thereby affect the risk of cardiovascular disease (CVD).ObjectiveIn the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad‐Stroke and Heart‐Atherosclerotic‐Disorders (MASHAD) cohort.MethodsOne thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow‐up. After a 12‐h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra‐ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using <jats:italic>χ</jats:italic><jats:sup>2</jats:sup> tests. Eventually, the statistical analysis was done by SPSS version 20.ResultsIndividuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01–2.02, <jats:italic>p</jats:italic> = 0.041). There was a 1.3‐fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non‐carriers (OR = 1.32, 95%CI = 1.06–1.72, <jats:italic>p</jats:italic> value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL‐C.ConclusionWe have found that a rs10789117 C&gt;A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malformations of cortical development: Fetal imaging and genetics","authors":"Lin‐Lin Wang, Ping‐Shan Pan, Hui Ma, Chun He, Zai‐Long Qin, Wei He, Jing Huang, Shu‐Yin Tan, Da‐Hua Meng, Hong‐Wei Wei, Ai‐Hua Yin","doi":"10.1002/mgg3.2440","DOIUrl":"https://doi.org/10.1002/mgg3.2440","url":null,"abstract":"BackgroundMalformations of cortical development (MCD) are a group of congenital disorders characterized by structural abnormalities in the brain cortex. The clinical manifestations include refractory epilepsy, mental retardation, and cognitive impairment. Genetic factors play a key role in the etiology of MCD. Currently, there is no curative treatment for MCD. Phenotypes such as epilepsy and cerebral palsy cannot be observed in the fetus. Therefore, the diagnosis of MCD is typically based on fetal brain magnetic resonance imaging (MRI), ultrasound, or genetic testing. The recent advances in neuroimaging have enabled the in‐utero diagnosis of MCD using fetal ultrasound or MRI.MethodsThe present study retrospectively reviewed 32 cases of fetal MCD diagnosed by ultrasound or MRI. Then, the chromosome karyotype analysis, single nucleotide polymorphism array or copy number variation sequencing, and whole‐exome sequencing (WES) findings were presented.ResultsPathogenic copy number variants (CNVs) or single‐nucleotide variants (SNVs) were detected in 22 fetuses (three pathogenic CNVs [9.4%, 3/32] and 19 SNVs [59.4%, 19/32]), corresponding to a total detection rate of 68.8% (22/32).ConclusionThe results suggest that genetic testing, especially WES, should be performed for fetal MCD, in order to evaluate the outcomes and prognosis, and predict the risk of recurrence in future pregnancies.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic analysis of nephrogenic diabetes insipidus patients: A study on the Iranian population","authors":"Saeed Ghasemi, Marzieh Mojbafan, Saeed Talebi, Nakysa Hooman, Rozita Hoseini","doi":"10.1002/mgg3.2421","DOIUrl":"https://doi.org/10.1002/mgg3.2421","url":null,"abstract":"Nephrogenic diabetes insipidus (NDI) is a rare genetic disease that causes water imbalance. The kidneys play a crucial role in regulating body fluids by controlling water balance through urine excretion. This highlights their essential function in managing the body's water levels, but individuals with NDI may have excess urine production (polyuria), that leads to excessive thirst (polydipsia). Untreated affected individuals may exhibit poor feeding and failure to thrive. This disease is caused by mutations in the <i>AVPR2</i> and the <i>AQP2</i> genes which have the X-linked and autosomal recessive/dominant inheritance, respectively. Both of these genes are expressed in the kidney.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140569130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}