Genetic testing led to the detection of an X-linked hemizygous truncating mutation in the nuclear polyglutamine-binding protein 1 (<i>PQBP1</i>) gene confirming the diagnosis of X-linked recessive Renpenning syndrome.<b>Conclusion</b>: The presence of X-linked intellectual disability and characteristic dysmorphism, in a patient with the MAC spectrum should raise the suspicion of Renpenning syndrome.
Whole exome sequencing identified a novel missense PQBP1 variant c.530G>A:p.R177H in the second family, in which the index patient presented with intellectual disability and dysmorphic facial features reminiscent of Kabuki-like syndrome and his brain magnetic resonance imaging revealed partial agenesis of corpus callosum, mild vermis, and brainstem hypoplasia.
Whole exome sequencing identified a novel missense PQBP1 variant c.530G>A:p.R177H in the second family, in which the index patient presented with intellectual disability and dysmorphic facial features reminiscent of Kabuki-like syndrome and his brain magnetic resonance imaging revealed partial agenesis of corpus callosum, mild vermis, and brainstem hypoplasia.
Here, we show that phosphorylation of serine/arginine repetitive matrix 2 (SRRM2) at Ser1068, which is observed in the brains of early phase AD mouse models and postmortem end-stage AD patients, prevents its nuclear translocation by inhibiting interaction with T-complex protein subunit α. SRRM2 deficiency in neurons destabilized polyglutamine binding protein 1 (PQBP1), a causative gene for intellectual disability (ID), greatly affecting the splicing patterns of synapse-related genes, as demonstrated in a newly generated PQBP1-conditional knockout model.
The WW domain belonging to polyglutamine tract-binding protein 1 (PQBP1) is of particular interest due to its direct involvement in several X chromosome-linked intellectual disabilities, including Golabi-Ito-Hall (GIH) syndrome, where a single point mutation (Y65C) correlates with the development of the disease.
Atypical microduplications allowed us to identify minimal critical regions that might be responsible for specific clinical findings of the syndrome and to suggest possible candidate genes: FTSJ1 and SHROOM4 for intellectual disability along with PQBP1 and SLC35A2 for epilepsy.
Mutations in the PQBP1 gene were reported in several X chromosome-linked intellectual disability (XLID) disorders, including Golabi-Ito-Hall (GIH) syndrome.
Together with previously reported observations, our data further confirm that PQBP1 gene should be tested for males showing mental retardation, short stature, lean body and microcephaly.
The polyglutamine-binding protein 1 (PQBP1) has been linked to several X-linked intellectual disability disorders and progressive neurodegenerative diseases.
For four mutations affecting ATRX (p.1761M>T), PQBP1 (p.155R>X) and SLC6A8 (p.390P>L and p.477S>L), we provide evidence for a functional involvement of these changes in the aetiology of intellectual disability.
PQBP1 (polyglutamine tract-binding protein 1) is a causative gene for a relatively frequent X-linked syndromic and non-syndromic mental retardation (MR).
Frame shift mutations of the polyglutamine binding protein-1 (PQBP1) gene lead to total or partial truncation of the C-terminal domain (CTD) and cause mental retardation in human patients.
This localisation overlaps MRXS3, a syndromic form of mental retardation resembling that found in the family described here, although with a milder presentation.