Disease relevance of GPR98

• The identification of additional VLGR1 mutations to test whether a phenotype/genotype correlation exists, akin to that shown for other Usher syndrome disease genes, is warranted [1].
• We screened for MASS1 mutations in individuals from 48 families with familial febrile seizures and found 25 DNA alterations [2].
• The molecular basis and pathophysiology of hearing loss suggest BUB/BnJ and Frings mice as models to study cellular and molecular mechanisms underlying USH2C auditory pathology [3].

High impact information on GPR98

• Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II [1].
• VLGR1 mutations have been previously identified in both humans and mice and are associated with a reflex-seizure phenotype in both species [1].
• The VLGR1 (MASS1) gene in the 5q14.3-q21.1 USH2C locus was considered a likely candidate on the basis of its protein motif structure and expressed-sequence-tag representation from both cochlear and retinal subtracted libraries [1].
• These findings indicate that there is a gene on chromosome 5q14-q15 that confers susceptibility to FSs and we call this gene FEB4 [4].
• Our results suggest that a loss-of-function mutation in MASS1 might be responsible for the seizure phenotypes, though it is not likely that MASS1 contributed to the cause of febrile seizures in most of our families [2].

Biological context of GPR98

• The human orthologous gene, MASS1, was mapped to chromosome 5q14, for which we previously have reported significant evidence of linkage to febrile seizures (FEB4) [2].
• Mutation analysis of the exons and exon-intron boundaries of MASS1 in our family did not reveal a disease causing mutation [5].
• It is 51% identical to human VLGR1 in amino acid sequence, but is 64% identical in the 7-transmembrane and cytoplasmic domains [6].

Anatomical context of GPR98

• CONCLUSIONS: USH2C and USH2A manifest photoreceptor disease with rod- and cone-mediated visual losses and thinning of the outer nuclear layer [7].

Other interactions of GPR98

• METHODS: Three siblings with USH2C and 14 patients with USH2A were studied [7].
• Genome-wide linkage of febrile seizures and epilepsy to the FEB4 locus at 5q14.3-q23.1 and no MASS1 mutation [5].

References