Evaluation of the reliability of the Cutaneous Dermatomyositis Disease Area and Severity Index and the Cutaneous Assessment Tool-Binary Method in juvenile dermatomyositis among paediatric dermatologists, rheumatologists and neurologists.

BACKGROUND: The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and Cutaneous Assessment Tool-Binary Method (CAT-BM) have been shown to be reliable and valid outcome measures to assess cutaneous disease in adult dermatomyositis (DM) and juvenile DM (JDM), respectively. OBJECTIVES: This study compared the CDASI and CAT-BM for use by paediatric dermatologists, paediatric rheumatologists and paediatric neurologists in patients with JDM. METHODS: Five paediatric dermatologists, five paediatric rheumatologists and five paediatric neurologists each evaluated 14 patients with JDM using the CDASI, CAT-BM, and skin Physician Global Assessment (PGA) scales. Inter-rater reliability, intra-rater reliability, construct validity and completion time were compared. RESULTS: Inter-rater reliability for CDASI activity and damage scores was good to moderate for paediatric dermatologists and rheumatologists, but poor for paediatric neurologists. The inter-rater reliability for CAT-BM activity scores was moderate for paediatric dermatologists and rheumatologists, but poor for paediatric neurologists and poor across all specialties for damage scores. Intra-rater reliability for the CDASI and CAT-BM activity and damage scores was moderate to excellent for paediatric dermatologists, rheumatologists and neurologists. Strong associations were found between skin PGA activity and damage scores and CDASI or CAT-BM activity and damage scores, respectively (P < 0·002). The CDASI had a mean completion time of 5·4 min compared with that for the CAT-BM of 3·1 min. CONCLUSIONS: Our data confirm the reliability of the CDASI activity and damage scores and the CAT-BM activity scores when used by paediatric dermatologists and rheumatologists in assessing JDM. Significant variation existed in the paediatric neurologists' scores.

Familial dysautonomia is caused by mutations of the IKAP gene.

The defective gene DYS, which is responsible for familial dysautonomia (FD) and has been mapped to a 0.5-cM region on chromosome 9q31, has eluded identification. We identified and characterized the RNAs encoded by this region of chromosome 9 in cell lines derived from individuals homozygous for the major FD haplotype, and we observed that the RNA encoding the IkappaB kinase complex-associated protein (IKAP) lacks exon 20 and, as a result of a frameshift, encodes a truncated protein. Sequence analysis reveals a T-->C transition in the donor splice site of intron 20. In individuals bearing a minor FD haplotype, a missense mutation in exon 19 disrupts a consensus serine/threonine kinase phosphorylation site. This mutation results in defective phosphorylation of IKAP. These mutations were observed to be present in a random sample of Ashkenazi Jewish individuals, at approximately the predicted carrier frequency of FD. These findings demonstrate that mutations in the gene encoding IKAP are responsible for FD.