ANALYSIS OF GLRA1 IN HEREDITARY AND SPORADIC HYPEREKPLEXIA - A NOVEL MUTATION IN A FAMILY COSEGREGATING FOR HYPEREKPLEXIA AND SPASTIC PARAPARESIS

Hyperekplexia is a rare condition characterised by the presence of neo natal hypertonia and an exaggerated startle response. Mutations have b een described in GLRA1, the gene encoding the alpha 1 subunit of the g lycine receptor, in dominant families with hyperekplexia and in a sing le sporadic case, thought to represent an autosomal recessive form of the disease. In this study the coding region of the GLRA1 was analysed in eight probands with hyperekplexia by restriction digest and sequen cing. Two familial cases were found to possess the previously describe d G1192A (R271Q) mutation in exon 6. In an additional family in which hyperekplexia cosegregates with spastic paraparesis, a novel A to G tr ansversion at nucleotide 1206 in exon 6 was detected that changes a ly sine at amino acid 276 to a glutamate (K276E). In four sporadic cases no mutations were found. In addition, one familial case did not have a mutation in the coding region of the gene.