Related Experiment Video
Updated: Mar 22, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Deleterious mutation in GPR88 is associated with chorea, speech delay, and learning disabilities
Fadi Alkufri1, Avraham Shaag1, Bassam Abu-Libdeh1
1Department of Neurosciences (F.A.) and Department of Pediatrics (B.A.-L.), Al-Makassed Islamic Hospital, Jerusalem, Israel; and Monique and Jacques Roboh Department of Genetic Research (A.S., O.E.), Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Objective:
To identify the underlying molecular basis of a familial developmental disorder characterized by chorea, marked speech delay, and learning difficulties in 4 sisters from a consanguineous family.
Methods:
Whole-exome analysis of DNA of the 2 older patients followed by Sanger sequencing of the mutated exon in all family members.
Results:
A homozygous deleterious mutation, p.C291X, was identified in the GPR88 gene in both exome analyses. The mutation segregated with the disease in the family and was absent from a large cohort of controls.
Conclusions:
Homozygous deleterious mutation in GPR88 in humans is associated with marked speech delay, learning disabilities, and chorea, which manifest at 8-9 years of age. The finding is consistent with the reported abundant expression of GPR88 in the striatum and the hyperkinetic activity and learning impairment observed in GPR88 knockout mice. Although further functional characterization is needed, the finding underscores the importance of GPR88 in movement control and learning.
More Related Videos
08:22A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene
Published on: September 16, 2019
11:46Investigating Protein-protein Interactions in Live Cells Using Bioluminescence Resonance Energy Transfer
Published on: May 26, 2014
Related Concept Videos
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
02:18Alternative RNA Splicing
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
01:33Pleiotropy