This report describes Kleefstra syndrome 1 (KLEFS1), which is a subtype of Kleefstra syndrome; KLEFS1 exhibits an autosomal dominant pattern of inheritance. OMIM also includes KLEFS1 in the phenotypic series for autosomal dominant intellectual disability (FBhh0000127). Originally mapped to a small deletion on chromosome 9, it has been determined that the specific gene implicated in Kleefstra syndrome is euchromatic histone methyltransferase 1 (EHMT1). There is a single moderate-scoring ortholog of EHMT1 in Drosophila, G9a, for which loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\G9a is also orthologous to a second gene in human, EHMT2.
The human EHMT1 gene has not been introduced into flies.
Animals homozygous for amorphic alleles of Dmel\G9a are viable and fertile. Larvae exhibit locomotor defects and abnormalities in dendrite development. Adults exhibit defects in non-associative learning and courtship memory; memory is restored by G9a expression during adulthood. A small number of physical and genetic interactions have been described for Dmel\G9a; see below and in the G9a gene report. It is proposed that G9a/EHMT1 plays a key role in a highly conserved epigenetic network that impacts cognition and memory.
[updated Jan. 2018 by FlyBase; FBrf0222196]
Kleefstra syndrome is characterized by developmental delay and variable intellectual disability, with other symptoms characteristic of the specific subtype.
[KLEEFSTRA SYNDROME 1; KLEFS1](https://omim.org/entry/610253)
[EUCHROMATIC HISTONE METHYLTRANSFERASE 1; EHMT1](https://omim.org/entry/607001)
Kleefstra syndrome 1 is characterized by developmental delay and intellectual disability, severely limited or absent speech, hypotonia, and characteristic facial features; heart defects or seizures are observed in some cases.
Kleefstra syndrome 1 is caused by heterozygous mutation in the EHMT1 gene, which is located within the region of the chromosome 9q34.3 deletion that was originally associated with this syndrome. [from MIM:610253; 2018.02.02]
EHMT1 (euchromatic histone methyltransferase 1) is a component of the E2F6 complex, which represses transcription and contributes to silencing of specific genes in quiescent cells. [from MIM:607001, MIM:602944; 2017.06.12]
Many to one: 2 human to 1 Drosophila.
Moderate-scoring ortholog of human EHMT1 and EHMT2 (1 Drosophila to 2 human); Dmel\G9a shares 26-28% identity and 41-42% similarity with the human genes.
