Dataset Information

Expanding the Phenotype and Genetic Defects Associated with the GOSR2 Gene.

ABSTRACT: Background:The homozygous missense mutation c.430G>T (p.G144W) in the GOSR2 gene has been repeatedly shown to cause progressive myoclonus epilepsy/ataxia. Thus far, no other disease associated GOSR2 mutation has been reported. Methods:From epilepsy, movement disorder and genetic clinics 43 patients suffering from progressive myoclonus epilepsy/ataxia were screened for defects in GOSR2, SCARB2 and CSTB. Results:A 61-year-old female patient suffering from progressive myoclonus epilepsy was found to be compound heterozygous for the known c.430G>T and a novel c.491_493delAGA (p.K164del) GOSR2 mutation. This is so far the oldest GOSR2 patient and her disease course seems overall milder. Conclusions:This finding further highlights the GOSR2 gene as a cause of progressive myoclonus epilepsy and expands the genotype for a potentially weaker disease allele.

SUBMITTER: Praschberger R

PROVIDER: S-EPMC6178697 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Expanding the Phenotype and Genetic Defects Associated with the <i>GOSR2</i> Gene.

Praschberger Roman R Balint Bettina B Mencacci Niccolo E NE Hersheson Joshua J Rubio-Agusti Ignacio I Kullmann Dimitri M DM Bettencourt Conceição C Bhatia Kailash K Houlden Henry H

Movement disorders clinical practice 20150617 3

<h4>Background</h4>The homozygous missense mutation c.430G>T (p.G144W) in the <i>GOSR2</i> gene has been repeatedly shown to cause progressive myoclonus epilepsy/ataxia. Thus far, no other disease associated <i>GOSR2</i> mutation has been reported.<h4>Methods</h4>From epilepsy, movement disorder and genetic clinics 43 patients suffering from progressive myoclonus epilepsy/ataxia were screened for defects in <i>GOSR2, SCARB2</i> and <i>CSTB</i>.<h4>Results</h4>A 61-year-old female patient sufferi ...[more]

PMID: 30363482

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Project description:BACKGROUND: Heterozygous copy-number and missense variants in CNTNAP2 and NRXN1 have repeatedly been associated with a wide spectrum of neuropsychiatric disorders such as developmental language and autism spectrum disorders, epilepsy and schizophrenia. Recently, homozygous or compound heterozygous defects in either gene were reported as causative for severe intellectual disability. METHODS: 99 patients with severe intellectual disability and resemblance to Pitt-Hopkins syndrome and/or suspected recessive inheritance were screened for mutations in CNTNAP2 and NRXN1. Molecular karyotyping was performed in 45 patients. In 8 further patients with variable intellectual disability and heterozygous deletions in either CNTNAP2 or NRXN1, the remaining allele was sequenced. RESULTS: By molecular karyotyping and mutational screening of CNTNAP2 and NRXN1 in a group of severely intellectually disabled patients we identified a heterozygous deletion in NRXN1 in one patient and heterozygous splice-site, frameshift and stop mutations in CNTNAP2 in four patients, respectively. Neither in these patients nor in eight further patients with heterozygous deletions within NRXN1 or CNTNAP2 we could identify a defect on the second allele. One deletion in NRXN1 and one deletion in CNTNAP2 occurred de novo, in another family the deletion was also identified in the mother who had learning difficulties, and in all other tested families one parent was shown to be healthy carrier of the respective deletion or mutation. CONCLUSIONS: We report on patients with heterozygous defects in CNTNAP2 or NRXN1 associated with severe intellectual disability, which has only been reported for recessive defects before. These results expand the spectrum of phenotypic severity in patients with heterozygous defects in either gene. The large variability between severely affected patients and mildly affected or asymptomatic carrier parents might suggest the presence of a second hit, not necessarily located in the same gene.

Dataset Information

Expanding the Phenotype and Genetic Defects Associated with the GOSR2 Gene.

Publications

Expanding the Phenotype and Genetic Defects Associated with the <i>GOSR2</i> Gene.

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