This report describes macrocephaly-autism syndrome; this disease exhibits autosomal dominant inheritance. The human gene implicated in macrocephaly-autism syndrome is PTEN, a lipid and protein phosphatase with diverse regulatory functions. There is a single orthologous gene in Drosophila, Dmel\Pten, for which an extensive collection of genetic reagents has been generated, including loss-of-function mutations, RNAi-targeting constructs, alleles caused by insertional mutagenesis, and overexpression constructs.
UAS constructs of the wild-type human Hsap\PTEN gene have been introduced into flies; heterologous rescue (functional complementation) has been demonstrated for the overgrowth phenotype of hypomorphic mutations of Dmel\Pten. Recently, a large number of mutations analogous to variants implicated in human disease have been introduced as transgenic Hsap\PTEN constructs. See the 'Disease-Implicated Variants' table, below, for tested variants associated with macrocephaly-autism syndrome. See the Hsap\PTEN gene report for a complete list of tested variants.
There are over 100 missense and nonsense mutations of human PTEN implicated in several different diseases. As part of a large-scale assessment of such variants an assay in Drosophila was employed. Ubiquitous expression of wild-type Hsap\PTEN results in delayed eclosion; expression of a complete loss-of-function variant of Hsap\PTEN does not. This allows an assessment of degree of wild-type function for PTEN variants found in human; 86 variants have been assessed in this assay.
[updated Apr.2024 by FlyBase; FBrf0222196]
[MACROCEPHALY/AUTISM SYNDROME](https://omim.org/entry/605309)
[PHOSPHATASE AND TENSIN HOMOLOG; PTEN](https://omim.org/entry/601728)
Macrocephaly/autism syndrome is an autosomal dominant disorder characterized by increased head circumference, abnormal facial features, and delayed psychomotor development resulting in autistic behavior or mental retardation (Herman et al., 2007; pubmed:17286265). Some patients may have a primary immunodeficiency disorder with recurrent infections associated with variably abnormal T- and B-cell function (Tsujita et al., 2016; pubmed:27426521). [from MIM:605309; 2020.09.14]
Macrocephaly/autism syndrome is caused by heterozygous mutation in the PTEN gene. [from MIM:605309; 2020.09.14]
The PTEN gene encodes a ubiquitously expressed tumor suppressor dual-specificity phosphatase that antagonizes the PI3K signaling pathway through its lipid phosphatase activity and negatively regulates the MAPK pathway through its protein phosphatase activity (summary by Pezzolesi, et al., 2007; pubmed:17341483). [from MIM:601728; 2020.09.14]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human PTEN (1 Drosophila to 1 human). Dmel\Pten shares 39% identity and 54% similarity with the human gene.
