Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition.

BACKGROUND: A novel autosomal recessive condition, dilated cardiomyopathy with ataxia (DCMA) syndrome, has been identified in the Canadian Dariusleut Hutterite population, characterised by early onset dilated cardiomyopathy with conduction defects, non-progressive cerebellar ataxia, testicular dysgenesis, growth failure, and 3-methylglutaconic aciduria. OBJECTIVE: To map DCMA syndrome and identify the mutation underlying this condition. METHODS: A genome wide scan was undertaken on consanguineous Hutterite families using a homozygosity mapping approach in order to identify the DCMA associated chromosomal region. Mutation analysis was carried out on positional candidate genes in this region by sequencing. Reverse transcriptase polymerase chain reaction and bioinformatics analyses were then used to characterise the mutation and determine its effect on the protein product. RESULTS: The association of DCMA syndrome with a 2.2 Mb region of chromosome 3q26.33 was found. A disease associated mutation was identified: IVS3-1 G-->C in the DNAJC19 gene, encoding a DNAJ domain containing protein of previously unknown function (Entrez Gene ID 131118). CONCLUSIONS: The DNAJC19 protein was previously localised to the mitochondria in cardiac myocytes, and shares sequence and organisational similarity with proteins from several species including two yeast mitochondrial inner membrane proteins, Mdj2p and Tim14. Tim14 is a component of the yeast inner mitochondrial membrane presequence translocase, suggesting that the unique phenotype of DCMA may be the result of defective mitochondrial protein import. It is only the second human disorder caused by defects in this pathway that has been identified.

The Development and Psychometric Properties of the MSQOL: A Migraine-Specific Quality-of-Life Instrument.

This paper describes the development and testing of the UK version of the Migraine-Specific Quality-of-Life instrument (MSQOL), a measure designed to assess the quality of life of migraineurs. The work was part of an international research study conducted in eight countries, with the initial development work conducted in the UK and the USA. In the UK, interviews were held with 30 patients with migraine, while in the USA, 25 individual interviews were conducted, along with one focus group with 5 participants. Transcripts were produced of the interviews/group discussion and these were used to determine the questionnaire items, which were then considered by an international translation panel. The panel considered the feasibility of translating the items into other European languages. The instrument was then assessed for reliability and validity. The UK version of the MSQOL was shown to have excellent test-retest reliability (0.93 over 2 weeks) and internal consistency (0.92 and 0.93 on the first and second administrations, respectively). Scores on the measure were also found to be related to a comparator measure of well-being and to perceived severity of migraine and disruption caused to patients by the disease. Findings for the other language versions of the MSQOL supported those from the UK, suggesting that the instrument may well be suitable for inclusion in clinical trials.