• brachycephaly, trichomegaly, and developmental delay

This report describes brachycephaly, trichomegaly, and developmental delay (BTDD), also known as MacInnes syndrome; BTDD exhibits autosomal dominant inheritance. The gene implicated in this disease is RPS23, which encodes a ribosomal protein that is a component of the small 40S subunit. There is a single orthologous gene in Drosophila, RpS23, for which RNAi-targeting constructs have been generated.

The human RPS23 gene has not been introduced into flies.

An RPS23 variant implicated in BTDD has been introduced into the fly RpS23 gene in situ. Variant(s) implicated in human disease introduced (as analogous mutation in fly gene): R67K in the fly RpS23 gene (corresponds to R67K in the human RPS23 gene). Animals heterozygous for the R67K mutation exhibit the classic loss-of-function Minute phenotype observed for mutations affecting ribosomal genes in Drosophila. As has been observed for mutations in other ribosomal genes, in mosaic imaginal discs RpS23^R67K/+ cells are outcompeted by surrounding wild-type cells. Using this system and other genotypes with heterozygous loss-of-function ribosomal protein genes, widespread apoptosis and cellular stress is observed; it is suggested that this is caused by accumulation of misfolded proteins that overwhelm the protein degradation pathways.

[updated Feb. 2021 by FlyBase; FBrf0222196]