Using whole-exome sequencing, we have identified novel de novo heterozygous pleckstrin homology domain-interacting protein (<i>PHIP</i>) variants that are predicted to be deleterious, including a frameshift deletion, in two unrelated patients with common clinical features of developmental delay, intellectual disability, anxiety, hypotonia, poor balance, obesity, and dysmorphic features.
We investigated a family of three boys with intellectual disability, and among them we identified two different mutations in KDM5C, located at Xp11.22, using whole-exome sequencing.
We investigated a family of three boys with intellectual disability, and among them we identified two different mutations in KDM5C, located at Xp11.22, using whole-exome sequencing.
Mutation analysis of the JARID1C gene was conducted in the following cohorts: probands from 23 XLMR families linked to Xp11.2, 92 males with mental retardation and short stature, and 172 probands from small XLMR families with no linkage information.
This family provides strong evidence that homozygous PRRT2 mutations give rise to more severe clinical disease of mental retardation, episodic ataxia, and absences, and, thus, enlarges the clinical spectrum related to PRRT2 mutations.
Our results uncover a biological role for TRMT1-catalyzed tRNA modification in redox metabolism and show that individuals with TRMT1-associated ID are likely to have major perturbations in cellular homeostasis due to the lack of m2,2G modifications.
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.
This study shows that PHF21A haploinsufficiency results in intellectual disability and craniofacial anomalies and possibly contributes to susceptibility to autism spectrum disorder, epilepsy, and overgrowth, all of which are PSS features.
Finally, a constitutional de novo mutation of MTOR (p.Glu1799Lys) was identified in 3 unrelated children with diffuse megalencephaly and intellectual disability.