Mutational analysis of familial and sporadic hyperekplexia

Hyperekplexia is a rare, autosomal dominant neurological disorder characterized by hypertonia, especially in infancy, and by an exaggerated startle response. This disorder is caused by mutations in the ?1 subunit of the inhibitory glycine receptor (GLRA1). We previously reported two GLRA1 point mutations detected in 4 unrelated hyperekplexia families; both mutations were at nucleotide 1192 and resulted in the replacement of Arg²⁷¹ by a glutamine (R271Q) in one case and a leucine (R271L) in the other. Here, 5 additional hyperekplexia families are shown to have the most common G-to-A transition mutation at nucleotide 1192. Haplotype analysis using polymorphisms within and close to the GLRA1 locus suggests that this mutation has arisen at least twice (and possibly four times). In 2 additional families, a third mutation is also presented that changes a tyrosine at amino acid 279 to a cysteine (Y279C). Five patients with atypical clinical features and equivocal or absent family history of hyperekplexia and 1 patient with a classical presentation but no family history are presented in whom a mutation in the GLRA1 gene was not detected. Thus, only clinically typical hyperekplexia appears to be consistently associated with GLRA1 mutations, and these affect a specific extracellular domain of the protein.     

Two cases of hereditary keratoderma with congenital glaucoma

Two cases are reported: a father and son with a new syndrome consisting of a severe congenital glaucoma associated with a form of palmoplantar keratoderma showing features of mutilating palmoplantar keratoderma. Both the glaucoma and keratoderma may be attributed to an autosomal dominantly inherited genetic mutation of a single chromosome affecting two tissues of neural crest origin, the ectodermal tissues of the hands and feet and the cranial mesenchyme from which the tissues of the chamber angle develop. Elucidation of the precise chromosomal abnormality causing these defects may help in understanding the inheritance and aetiology of glaucoma.     

A questionnaire examining learning in general practice

Vocational training is a key element of professional development in general practice. Learner-centred approaches to teaching bring a need for greater understanding of the individual learning styles and preferences of trainees. This paper reports the findings of a pilot study undertaken to determine factors that may influence learning among general practice trainees. A questionnaire survey of 261 trainees in six regions in the UK was carried out to explore attitudes to a series of themes identified in semi-structured interviews with trainees at the end of their training. Six distinct subscales were identified using principal components analysis. These are named 'Learning from Patients', 'Openness to Criticism', 'Negative Attitudes', 'Desire for Clear Guidelines', 'Peer Support', and 'Academic Approach'. Males scored significantly higher on 'Academic Approach' (   P < 0.05  ). Each of the subscales reflects themes that permeate the atmosphere of general pratice training. Further work is required to establish relationships between the subscales and the outcomes of learning and to explore the implications for continuing professional development. The questionnaire is an instrument that may prove useful in the future investigation of learning in general practice.