Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.
Ontology highlight
ABSTRACT:
SUBMITTER: Barel O
PROVIDER: S-EPMC2495061 | biostudies-literature | 2008 Aug
REPOSITORIES: biostudies-literature
Publications
Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9.
Barel Ortal O Shalev Stavit A SA Ofir Rivka R Cohen Asi A Zlotogora Joel J Shorer Zamir Z Mazor Galia G Finer Gal G Khateeb Shareef S Zilberberg Noam N Birk Ohad S OS
American journal of human genetics 20080801 2
We describe a maternally transmitted genomic-imprinting syndrome of mental retardation, hypotonia, and unique dysmorphism with elongated face. We mapped the disease-associated locus to approximately 7.27 Mb on chromosome 8q24 and demonstrated that the disease is caused by a missense mutation in the maternal copy of KCNK9 within this locus. KCNK9 is maternally transmitted (imprinted with paternal silencing) and encodes K(2P)9.1, a member of the two pore-domain potassium channel (K(2P)) subfamily. ...[more]
Similar Datasets
Project description:Congenital hypoparathyroidism, growth retardation and facial dysmorphism is a rare autosomal recessive disorder seen among children born to consanguineous couple of Arab ethnicity. This syndrome is commonly known as Sanjad-Sakati or hypoparathyroidism-retardation-dysmorphism syndrome (HRD). We report 13-year-old Hindu boy with hypoparathyroidism, tetany, facial dysmorphism and developmental delay, compatible with HRD syndrome.
| S-EPMC3841568 | biostudies-literature
Project description:A functional role for DNA methylation has been well-established at imprinted loci, which inherit methylation uniparentally, most commonly from the mother via the oocyte. Many CpG islands not associated with imprinting also inherit methylation from the oocyte, although the functional significance of this, and the common features of the genes affected, are unclear. We identify two major subclasses of genes associated with these gametic differentially methylated regions (gDMRs), namely those important for brain and for testis function. The gDMRs at these genes retain the methylation acquired in the oocyte through preimplantation development, but become fully methylated postimplantation by de novo methylation of the paternal allele. Each gene class displays unique features, with the gDMR located at the promoter of the testis genes but intragenically for the brain genes. Significantly, demethylation using knockout, knockdown or pharmacological approaches in mouse stem cells and fibroblasts resulted in transcriptional derepression of the testis genes, indicating that they may be affected by environmental exposures, in either mother or offspring, that cause demethylation. Features of the brain gene group suggest that they might represent a pool from which many imprinted genes have evolved. The locations of the gDMRs, as well as methylation levels and repression effects, were also conserved in human cells.
| S-EPMC3943183 | biostudies-literature
Project description:Differences in chromatin state inherited from the parental gametes influence the regulation of maternal and paternal alleles in offspring. This phenomenon, known as genomic imprinting, results in genes preferentially transcribed from one parental allele. While local epigenetic factors such as DNA methylation are known to be important for the establishment of imprinted gene expression, less is known about the mechanisms by which differentially methylated regions (DMRs) lead to differences in allelic expression across broad stretches of chromatin. Allele-specific higher-order chromatin structure has been observed at multiple imprinted loci, consistent with the observation of allelic binding of the chromatin-organizing factor CTCF at multiple DMRs. However, whether allelic chromatin structure impacts allelic gene expression is not known for most imprinted loci. Here we characterize the mechanisms underlying brain-specific imprinted expression of the Peg13-Kcnk9 locus, an imprinted region associated with intellectual disability. We performed region capture Hi-C on mouse brains from reciprocal hybrid crosses and found imprinted higher-order chromatin structure caused by the allelic binding of CTCF to the Peg13 DMR. Using an in vitro neuron differentiation system, we showed that imprinted chromatin structure precedes imprinted expression at the locus. Additionally, activation of a distal enhancer induced imprinted expression of Kcnk9 in an allelic chromatin structure-dependent manner. This work provides a high-resolution map of imprinted chromatin structure and demonstrates that chromatin state established in early development can promote imprinted expression upon differentiation.
| S-EPMC10620047 | biostudies-literature
Project description:Differences in chromatin state inherited from the parental gametes influence the regulation of maternal and paternal alleles in offspring. This phenomenon, known as genomic imprinting, results in genes preferentially transcribed from one parental allele. While local epigenetic factors such as DNA methylation are known to be important for the establishment of imprinted gene expression, less is known about the mechanisms by which differentially methylated regions (DMRs) lead to differences in allelic expression across broad stretches of chromatin. Allele-specific higher-order chromatin structure has been observed at multiple imprinted loci, consistent with the observation of allelic binding of the chromatin-organizing factor CTCF at multiple DMRs. However, whether allelic chromatin structure impacts allelic gene expression is not known for most imprinted loci. Here we characterize the mechanisms underlying brain-specific imprinted expression of the Peg13-Kcnk9 locus, an imprinted region associated with intellectual disability. We performed region capture Hi-C on mouse brain from reciprocal hybrid crosses and found imprinted higher-order chromatin structure caused by the allelic binding of CTCF to the Peg13 DMR. Using an in vitro neuron differentiation system, we show that on the maternal allele enhancer-promoter contacts formed early in development prime the brain-specific potassium leak channel Kcnk9 for maternal expression prior to neurogenesis. In contrast, these enhancer-promoter contacts are blocked by CTCF on the paternal allele, preventing paternal Kcnk9 activation. This work provides a high-resolution map of imprinted chromatin structure and demonstrates that chromatin state established in early development can promote imprinted expression upon differentiation.
| S-EPMC10274912 | biostudies-literature
Project description:Early development depends heavily on accurate control of maternally inherited mRNAs, and yet it remains unknown how maternal microRNAs are regulated during maternal-to-zygotic transition (MZT). We here find that maternal microRNAs are highly adenylated at their 3' ends in mature oocytes and early embryos. Maternal microRNA adenylation is widely conserved in fly, sea urchin, and mouse. We identify Wispy, a noncanonical poly(A) polymerase, as the enzyme responsible for microRNA adenylation in flies. Knockout of wispy abrogates adenylation and results in microRNA accumulation in eggs, whereas overexpression of Wispy increases adenylation and reduces microRNA levels in S2 cells. Wispy interacts with Ago1 through protein-protein interaction, which may allow the effective and selective adenylation of microRNAs. Thus, adenylation may contribute to the clearance of maternally deposited microRNAs during MZT. Our work provides mechanistic insights into the regulation of maternal microRNAs and illustrates the importance of RNA tailing in development.
| S-EPMC4378961 | biostudies-literature
Project description:BackgroundAlthough the mitochondrial DNA (mtDNA) mutations m.1555A > G and m.3243A > G are the primary causes of maternally inherited sensorineural hearing loss (SNHL), several other mtDNA mutations are also reported to be associated with SNHL.MethodsScreening of m.1555A > G and m.3243A > G mutations was performed for 145 probands. Nine probands fulfilled the following criteria: 1) bilateral and symmetric SNHL, 2) ≥ 4 family members with SNHL with a maternal trait of inheritance in ≥ 2 generations, 3) onset of SNHL before the age of 40 years, 4) high-frequency SNHL, and 5) no record of environmental factors related to SNHL. Sequencing of additional mtDNA regions was performed for five subjects meeting the clinical criteria, but the screening results were negative.ResultsAmong the nine cases meeting the five clinical criteria detailed above, three had the m.1555A > G mutation in MTRNR1, one had a m.3243A > G mutation in MTTL1, and one case had a m.7511T > C mutation in MTTS1. In the family with the m.7511T > C mutation, penetrance of SNHL among maternally related subjects was 9/17 (53%). The age at onset varied from birth (congenital) to adulthood. Hearing levels varied from normal to moderately impaired, unlike previously reported subjects with this mutation, where some maternal family members presented with profound SNHL. Family members with the m.7511T > C mutation and SNHL did not exhibit any specific clinical characteristics distinct from those of other individuals with SNHL and different mtDNA mutations. Among the 136 probands who did not meet the criteria detailed above, one case had the m.1555A > G mutation, and three cases had the m.3243A > G mutation.ConclusionsSince five of nine probands with the clinical criteria used in this study had mtDNA mutations, these criteria may be helpful for identification of candidate patients likely to have mtDNA mutations.
| S-EPMC5359870 | biostudies-literature
Project description:Most mammals rely on chemosensory cues for individual recognition, which is essential to many aspects of social behavior, such as maternal bonding, mate recognition, and inbreeding avoidance. Both volatile molecules and nonvolatile peptides secreted by individual conspecifics are detected by olfactory sensory neurons in the olfactory epithelium and the vomeronasal organ. The pertinent cues used for individual recognition remain largely unidentified. Here we show that nonformylated, but not N-formylated, mitochondrially encoded peptides-that is, the nine N-terminal amino acids of NADH dehydrogenases 1 and 2-can be used to convey strain-specific information among individual mice. We demonstrate that these nonformylated peptides are sufficient to induce a strain-selective pregnancy block. We also observed that the pregnancy block by an unfamiliar peptide derived from a male of a different strain was prevented by a memory formed at the time of mating with that male. Our findings also demonstrate that pregnancy-blocking chemosignals in the urine are maternally inherited, as evidenced by the production of reciprocal sons from two inbred strains and our test of their urine's ability to block pregnancy. We propose that this link between polymorphic mitochondrial peptides and individual recognition provides the molecular means to communicate an individual's maternal lineage and strain.
| S-EPMC7720231 | biostudies-literature
Project description:Mitochondrial respiratory chain disease represents one of the most common inborn errors of metabolism and is genetically heterogeneous, with biochemical defects arising from mutations in the mitochondrial genome (mtDNA) or the nuclear genome. As such, inheritance of mitochondrial respiratory chain disease can either follow dominant or recessive autosomal (Mendelian) inheritance patterns, the strictly matrilineal inheritance observed with mtDNA point mutations or X-linked inheritance. Parental consanguinity in respiratory chain disease is often assumed to infer an autosomal recessive inheritance pattern, and the analysis of mtDNA may be overlooked in the pursuit of a presumed nuclear genetic defect. We report the histochemical, biochemical and molecular genetic investigations of two patients with suspected mitochondrial disease who, despite being born to consanguineous first-cousin parents, were found to harbour well-characterised pathogenic mtDNA mutations, both of which were maternally transmitted. Our findings highlight that any diagnostic algorithm for the investigation of mitochondrial respiratory chain disease must include a full and complete analysis of the entire coding sequence of the mitochondrial genome in a clinically relevant tissue. An autosomal basis for respiratory chain disease should not be assumed in consanguineous families and that 'maternally inherited consanguineous' mitochondrial disease may thus be going undiagnosed.
| S-EPMC3230363 | biostudies-literature
Project description:Early development depends heavily on accurate control of maternally inherited mRNAs, and yet it remains unknown how maternal microRNAs (miRNAs) are regulated during maternal to zygotic transition (MZT). We here find that maternal miRNAs are highly adenylated at their 3' ends in mature oocytes and early embryos. Pervasive adenylation is observed in oocytes of fly, sea urchin and mouse, indicating that maternal miRNA adenylation may be widely conserved in animals. We identify Wispy as the enzyme responsible for miRNA adenylation in flies. Wispy is known to be expressed specifically in oocytes and early embryos and function as a noncanonical poly(A) polymerase. Knockout of wispy abrogates miRNA adenylation and induces miRNA accumulation in fly eggs whereas overexpression of Wispy increases adenylation and reduces miRNA levels in S2 cells. Adenylation occurs on both the 5p and 3p miRNAs, indicating that Wispy acts on miRNAs after Dicer processing. We further find that Wispy interacts with Ago1 through protein-protein interaction, which may allow the effective and selective adenylation of miRNAs. Thus, adenylation may contribute to the clearance of maternally deposited miRNAs during MZT. Our work provides the first mechanistic insights into the regulation of maternal miRNAs and illustrates the importance of RNA tailing in development. MiRNA expression and modification profile during early embryo development of fruit fly and zebra fish using high throughput sequencing
2014-10-01 | E-GEOD-61931 | biostudies-arrayexpress
Project description:In the teleost egg, the embryo is immersed in an extraembryonic fluid that fills the space between the embryo and the chorion and partially isolates it from the external environment, called the perivitelline fluid (PVF). The exact composition of the PVF remains unknown in vertebrate animals. The PVF allows the embryo to avoid dehydration, to maintain a safe osmotic balance and provides mechanical protection; however, its potential defensive properties against bacterial pathogens has not been reported. In this work, we determined the global proteomic profile of PVF in zebrafish eggs and embryos, and the maternal or zygotic origin of the identified proteins was studied. In silico analysis of PVF protein composition revealed an enrichment of protein classes associated with non-specific humoral innate immunity. We found lectins, protease inhibitors, transferrin, and glucosidases present from early embryogenesis until hatching. Finally, in vitro and in vivo experiments done with this fluid demonstrated that the PVF possessed a strong agglutinating capacity on bacterial cells and protected the embryos when challenged with the pathogenic bacteria Edwardsiella tarda. Our results suggest that the PVF is a primitive inherited immune extraembryonic system that protects the embryos from external biological threats prior to hatching.
| S-EPMC7564447 | biostudies-literature