This report describes Renpenning syndrome 1 (RENS1), which is one of the series of diseases classified as intellectual disability, X-linked, syndromic. RENS1 exhibits X-linked recessive inheritance. The human gene implicated in this disease is PQBP1, a nuclear polyglutamine-binding protein; the function and role of PQBP1 are not well characterized. There is a single Drosophila ortholog, Dmel\PQBP1, for which a loss-of-function insertional allele and multiple RNAi-targeting constructs have been generated.
UAS constructs of the wild-type human Hsap\PQBP1 gene have been introduced into flies, which were assessed for learning and behavioral defects. Variant(s) implicated in human disease tested (as transgenic human gene, PQBP1): the c.461_462dupAG (frameshift) variant (designated as Hsap\PQBP1dupAG.UAS.Tag:FLAG) has been introduced into flies.
Animals homozygous for a loss-of-function allele of Dmel\PQBP1 exhibit a learning-defective phenotype; both homozygous and heterozygous animals have a significantly shorter lifespan. Physical interactions of the Dmel\PQBP1 protein product have been described; see below and in the FlyBase gene report for Dmel\PQBP1.
[updated Sep. 2017 by FlyBase; FBrf0222196]
Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).
Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).
[RENPENNING SYNDROME 1; RENS1](https://omim.org/entry/309500)
[POLYGLUTAMINE-BINDING PROTEIN 1; PQBP1](https://omim.org/entry/300463)
Renpenning syndrome 1 (RENS1) is an X-linked mental retardation syndrome with clinically recognizable features, including microcephaly, short stature, small testes, and dysmorphic faces. [from MIM:309500; 2016.01.19]
Renpenning syndrome is caused by mutation in the polyglutamine-binding protein gene PQBP1; it is inherited as an X-linked recessive. [from MIM:309500; 2016.01.19]
PQBP1 is a nuclear polyglutamine-binding protein that contains a WW domain, a protein-protein interaction motif that has 2 conserved trp (W) residues (Waragai et al., 1999; pubmed:10332029). [from MIM:300463; 2016.01.19]
One to one: 1 human to 1 Drosophila.
Ortholog of human gene PQBP1 (1 Drosophila to 1 human). Dmel\PQBP1 shares 24% identity and 32% similarity with the human gene; the two characteristic tryptophans of the WW region are conserved.
