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| Mendeliome v2.448 | EHMT2 |
Richard Lin changed review comment from: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1. PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Episignature partially overlaps with Kleefstra syndrome 1 but was reported to form its own distinct profile. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes. PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients. Sources: Literature; to: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1. PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Episignature partially overlaps with Kleefstra syndrome 1 but was reported to form its own distinct profile. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with a patient derived variant (Ehmt2 +/del_1076-1079) recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes. PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients. Sources: Literature |
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| Mendeliome v2.448 | EHMT2 |
Richard Lin changed review comment from: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1. PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes. PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients. Sources: Literature; to: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1. PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Episignature partially overlaps with Kleefstra syndrome 1 but was reported to form its own distinct profile. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes. PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients. Sources: Literature |
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| Mendeliome v2.447 | EHMT2 |
Richard Lin changed review comment from: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1. PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, strcutural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips anrd protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assay show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients. Sources: Literature; to: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1. PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes. PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients. Sources: Literature |
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| Mendeliome v2.447 | EHMT2 |
Richard Lin gene: EHMT2 was added gene: EHMT2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EHMT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: EHMT2 were set to 42434347; 42386776; 39674972 Phenotypes for gene: EHMT2 were set to Kleefstra syndrome, MONDO:0012455, EHMT2-related Review for gene: EHMT2 was set to GREEN Added comment: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1. PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, strcutural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips anrd protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assay show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients. Sources: Literature |
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| Mendeliome v2.0 | EHMT1 | Gene migrated from ENSG00000181090 to ENSG00000181090 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1188 | EHMT1 | Zornitza Stark Marked gene: EHMT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1188 | EHMT1 | Zornitza Stark Gene: ehmt1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1188 | EHMT1 | Zornitza Stark Phenotypes for gene: EHMT1 were changed from to Kleefstra syndrome 1 (MIM#610253) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1187 | EHMT1 | Zornitza Stark Publications for gene: EHMT1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1186 | EHMT1 | Zornitza Stark Mode of inheritance for gene: EHMT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1185 | EHMT1 | Crystle Lee reviewed gene: EHMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19264732; Phenotypes: Kleefstra syndrome 1 (MIM#610253); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | EHMT1 |
Zornitza Stark gene: EHMT1 was added gene: EHMT1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: EHMT1 was set to Unknown |
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