This report describes Sotos syndrome 1 (SOTOS1); SOTOS1 exhibits autosomal dominant inheritance. The human gene implicated in this disease is NSD1, which encodes a histone methyltransferase that plays a role in transcriptional regulation. There is a single orthologous gene in Drosophila, Dmel\NSD, for which multiple genetic reagents have been generated, including RNAi-targeting constructs, overexpression constructs, and a targeted CRISPR knockout construct. Dmel\NSD is also orthologous to the human genes NSD2 and NSD3.
The human NSD1 gene has not been introduced into flies.
Animals homozygous for an amorphic mutation of Dmel\NSD survive to adulthood, but exhibit modest neurological dysfunctions, such as reduced memory performance and slight locomotor defects. Larvae are of increased size, a phenotype similar to the childhood overgrowth phenotype observed for SOTOS1; increased size is also observed for adults.
See also the human disease model report NSD1 duplication syndrome (FBhh0001298). As might be expected for the opposite genetic change, a key aspect of NSD1 duplication syndrome is reduced growth phenotypes.
[updated Jun. 2021 by FlyBase; FBrf0222196]
[SOTOS SYNDROME; SOTOS](https://omim.org/entry/117550)
[NUCLEAR RECEPTOR-BINDING SET DOMAIN PROTEIN 1; NSD1](https://omim.org/entry/606681)
Sotos syndrome is a neurologic disorder characterized by overgrowth from the prenatal stage through childhood, with advanced bone age, an unusual face with large skull, acromegalic features and pointed chin, occasional brain anomalies and seizures, and impaired intellectual development (summary by Kurotaki et al., 2002; pubmed:11896389). [from MIM:117550; 2021.06.29]
Sotos syndrome-1 (SOTOS1) is caused by heterozygous mutation in the NSD1 gene or by a deletion in the 5q35 region including genomic sequence in addition to the NSD1 gene. [from MIM:117550; 2021.06.29]
NSD1 encodes a histone methyltransferase that dimethylates Lys-36 of histone H3. The NSD1 protein acts a transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. [Gene Cards, NSD1; 2021.06.29]
Many to one: 3 human genes to 1 Drosophila gene.
Moderate- to high-scoring ortholog of human NSD3, NSD2, and NSD1 (1 Drosophila to 3 human). Dmel\NSD shares 25-27% identity and 40-42% similarity with the human genes. NSD1 encodes a significantly larger protein, with additional amino-terminal residues.
