Editor’s Choice December 2011
CDKN2A mutations in Greek melanoma patients
Three hundred and four single primary melanoma (SPM) cases and 16 genetically enriched cases [seven patients with multiple primary melanoma (MPM) and nine with familial melanoma (FM)] were evaluated. Germline CDKN2A mutations were detected in 10 of 304 SPM, in four of seven MPM and in two of nine FM cases. The most common mutation was a Northern European allele (p16 p.R24P) detected in eight individuals. Five previously unreported CDKN2A variants were identified as well as the first report of a CDK4 p.R24H substitution in a Greek family. This study supports a role for CDKN2A and CDK4 mutations in susceptibility to melanoma among Greek individuals.
Nikolaou V, Kang X, Stratigos A et al. Comprehensive mutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma. Br J Dermatol 2011; 165: 1219–22.
Blue-black rule: a simple dermoscopic clue to recognize pigmented nodular melanoma
Dermoscopic images of 283 histopathologically diagnosed pigmented nodular tumours were evaluated for the presence of standard melanoma criteria and for the presence of a new feature named blue-black (BB) colour. Presence of the BB feature had 78·2% sensitivity for melanoma compared with a sensitivity of 43·6% achieved by the standard melanoma criteria. A combined method based on the presence of either the BB feature or one (or more) of the standard melanoma criteria reached a sensitivity of 84·6%, with specificity of 80·5% and negative predictive value of 93·2%. The combined method gave specificity and positive predictive value for malignancy of 91·9% and 90·6%, respectively.
Argenziano G, Longo C, Cameron A et al.Blue-black rule: a simple dermoscopic clue to recognize pigmented nodular melanoma. Br J Dermatol 2011; 165: 1251–55.
JEB-H in the Netherlands
The diagnostic features of 22 patients with junctional epidermolysis bullosa, type Herlitz (JEB-H) in the Dutch Epidermolysis Bullosa Registry between 1988 and 2011 are reported. The mean lifespan was 5·8 months (range 0·5–32·6). Mutations were identified in all 22 patients, with a total of 11 different mutations in LAMB3, LAMC2 and LAMA3. Three novel splice site mutations in LAMB3 are reported. The incidence of JEB-H in the Netherlands is 4·0 new cases per million live births and the carrier frequency of a JEB-H mutation is 1 in 249.
Yuen WY, Lemmink HH, van Dijk-Bos KK et al. Herlitz junctional epidermolysis bullosa: diagnostic features, mutational profile, incidence and population carrier frequency in the Netherlands. Br J Dermatol 2011; 165: 1314–22.
GWAS suggest HDAC9 as a new candidate gene for male-pattern baldness
This genome-wide association study suggests that the histone deacetylase 9 (HDAC9) gene is the third male-pattern baldness [androgenetic alopecia (AGA)] susceptibility gene. A German sample of 581 severely affected cases and 617 controls was investigated. The most significant association signal was obtained for rs756853 which is located intronically in HDAC9. Fine-mapping and a family-based analysis revealed that rs756853 and the 6-kb distal rs2249817 were the most highly associated single nucleotide polymorphisms. The association finding was replicated in an independent Australian sample, when the analysis was restricted to severely affected cases and unaffected controls (P = 0·026). Analysis of rs2249817 in a combined sample of severely affected German and Australian cases and unaffected controls revealed a strong association signal (P = 9·09 x 10−8). Tissue expression studies demonstrated HDAC9 expression in various tissues, including tissues of relevance to AGA. Pathway analyses led to the hypothesis that HDAC9 plays a functional role in AGA via interaction with the androgen receptor gene.
Brockschmidt FF, Heilmann S, Ellis JA et al. Susceptibility variants on chromosome 7p21·1 suggest HDAC9 as a new candidate gene for male-pattern baldness. Br J Dermatol 2011; 165: 1293–302.