ArticleAmerican journal of human genetics2017
Mutations in TMEM260 Cause a Pediatric Neurodevelopmental, Cardiac, and Renal Syndrome.
Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Comparative efficacy of different drugs in acute heart failure with renal dysfunction: a systematic review and network meta-analysis.Frontiers in cardiovascular medicine · 2024Pooled it
- AMolecular syndromology · 2025Article
- Bi-allelic deleterious variants in SNAPIN, which encodes a retrograde dynein adaptor, cause a prenatal-onset neurodevelopmental disorder.American journal of human genetics · 2025Article
- RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS.Nature communications · 2025Article
- Clinical utility of runs of homozygosity in the identification of genetic causes in individuals with rare diseases.Genetics in medicine open · 2025Article
- Global View of Domain-Specific O-Linked Mannose Glycosylation in Glycoengineered Cells.Molecular & cellular proteomics : MCP · 2024Article
- Genome-Wide Association Analysis and Genetic Parameters for Egg Production Traits in Peking Ducks.Animals : an open access journal from MDPI · 2024Article
- The c.1617del variant of TMEM260 is identified as the most frequent single gene determinant for Japanese patients with a specific type of congenital heart disease.Journal of human genetics · 2024Article
- Genetic etiology of truncus arteriosus excluding 22q11.2 deletion syndrome and identification of c.1617del, a prevalent variant in TMEM260, in the Japanese population.Journal of human genetics · 2024Article
- Loss of the endoplasmic reticulum protein Tmem208 affects cell polarity, development, and viability.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Human Genetics of Truncus Arteriosus.Advances in experimental medicine and biology · 2024Review
- Protein O-mannosylation: one sugar, several pathways, many functions.Glycobiology · 2023Review
- The SHDRA syndrome-associated geneProceedings of the National Academy of Sciences of the United States of America · 2023Article
- A novel homozygous variant ofFrontiers in medicine · 2023Article
- Clinical impact of exome sequencing in the setting of a general pediatric ward for hospitalized children with suspected genetic disorders.Frontiers in genetics · 2022Article
- Update on the Classification and Pathophysiological Mechanisms of Pediatric Cardiorenal Syndromes.Children (Basel, Switzerland) · 2021Review
- Article
- Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases.Acta neuropathologica · 2020Article
- Article
- Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features.American journal of human genetics · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Despite the accelerated discovery of genes associated with syndromic traits, the majority of families affected by such conditions remain undiagnosed. Here, we employed whole-exome sequencing in two unrelated consanguineous kindreds with central nervous system (CNS), cardiac, renal, and digit abnormalities. We identified homozygous truncating mutations in TMEM260, a locus predicted to encode numerous splice isoforms. Systematic expression analyses across tissues and developmental stages validated two such isoforms, which differ in the utilization of an internal exon. The mutations in both families map uniquely to the long isoform, raising the possibility of an isoform-specific disorder. Consistent with this notion, RT-PCR of lymphocyte cell lines from one of the kindreds showed reduced levels of only the long isoform, which could be ameliorated by emetine, suggesting that the mutation induces nonsense-mediated decay. Subsequent in vivo testing supported this hypothesis. First, either transient suppression or CRISPR/Cas9 genome editing of zebrafish tmem260 recapitulated key neurological phenotypes. Second, co-injection of morphants with the long human TMEM260 mRNA rescued CNS pathology, whereas the short isoform was significantly less efficient. Finally, immunocytochemical and biochemical studies showed preferential enrichment of the long TMEM260 isoform to the plasma membrane. Together, our data suggest that there is overall reduced, but not ablated, functionality of TMEM260 and that attenuation of the membrane-associated functions of this protein is a principal driver of pathology. These observations contribute to an appreciation of the roles of splice isoforms in genetic disorders and suggest that dissection of the functions of these transcripts will most likely inform pathomechanism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.