Dataset Information

Deleterious mutation in GPR88 is associated with chorea, speech delay, and learning disabilities.

ABSTRACT:

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.

SUBMITTER: Alkufri F

PROVIDER: S-EPMC4830197 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Deleterious mutation in GPR88 is associated with chorea, speech delay, and learning disabilities.

Alkufri Fadi F Shaag Avraham A Abu-Libdeh Bassam B Elpeleg Orly O

Neurology. Genetics 20160309 3

<h4>Objective</h4>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.<h4>Methods</h4>Whole-exome analysis of DNA of the 2 older patients followed by Sanger sequencing of the mutated exon in all family members.<h4>Results</h4>A homozygous deleterious mutation, p.C291X, was identified in the GPR88 gene in both exome analyses. The mutation segregated with th ...[more]

PMID: 27123486

Similar Datasets

Project description:We are searching for common gene expression alteration in the hippocampus of animal models of learning disabilities and in post-mortem human tissues derived from patients with cognitive deficits. Our study has three phases. In phase I, we want to investigate the changes in gene expression in a transgenic mouse line that shows impairments in hippocampal-dependent learning. These animals are overexpressing the RNA-binding protein HuD in the forebrain under the control of the alpha CAMKinII promoter. For phase II, we plan to characterize the hippocampus of another animal model of learning disabilities: fetal alcohol exposed (FAE) rats. Last, for phase III, we would like to examine gene expression changes in the hippocampus and other tissues from patients with schizophrenia. To test our hypothesis, in phase 2 of our project, we propose to compare the pattern of gene expression in our mouse model with that in the hippocampus of rats prenatally exposed to alcohol (FAE model). Our hypothesis is that learning disabilities have common neural substrates regardless of the origin of the disability being genetic, environmental of a combination of these two. To test this hypothesis, we plan to examine the pattern of gene expression in the hippocampus of animals and humans with cognitive deficits and use bioinformatics tools to identify common changes in gene expression in three of such conditions: a genetic model (HuD transgenic mice), an environmental model (FAE rats) and a model for combined environmental and genetic effects (patients with schizophrenia). All the animals are adult male Sprague-Dawley rats (age 90-100 days). Animals were divided in three diet groups and three experimental treatment conditions (9 conditions altogether). Three groups of pregnant rat dams were placed on different diet regimens: a liquid diet containing 5% alcohol (A) groups, a control group fed an isocaloric liquid diet without alcohol (B) and a group of rats fed lab chow ad libitum (C). Offspring from each of these groups were allowed to grow until adulthood and placed into each of three training groups: a contextual fear conditioned group (1), a non-learning stress control group (2) and a naive/unhandled group (3). Hippocampi were dissected and used to isolate total RNA from each rat diet and training condition. Initially, we will submit 18 samples as follows: 10 samples from training group 1 and 8 samples from training group 3 (training group 2 will be analyzed at a later date). The diet assignment for the 18 samples is: 8 samples from group A, 6 samples of group B and 4 samples of group C. Please note that I was able to enter only the first 8 samples, as the sample list does not hold 18 samples altogether. Keywords: dose response

Dataset Information

Deleterious mutation in GPR88 is associated with chorea, speech delay, and learning disabilities.

Objective

Methods

Results

Conclusions

Publications

Deleterious mutation in GPR88 is associated with chorea, speech delay, and learning disabilities.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure