Figure 1.
Pedigrees of the Chinese WS2 families WS01, WS02, and WS03, and audiograms of some affected male and female subjects.
High clinical variability was observed even within the same family. Not all affected persons manifested all clinical features. Circle, female; square, male; filled quadrants indicate phenotype associated with WS, upper left, premature graying hair; lower left, freckles on the skin; upper right, hearing loss; lower right, heterochromia iridis; arrow, the proband; *, DNA samples available.
Figure 2.
Photographs of some affected individuals.
Upper left, the proband of family WS13 presented with complete heterochromia iridis. Lower left, the proband of family WS04 presented with bilateral blue irides and special brown freckles on the face. Upper right, the proband of family WS08 presented with bilateral characteristic brilliant blue irides. Lower right, individual II:7 of family WS01 had numerous freckles on the dorsum of the hands. (The subjects in the photographs provided written informed consent for publication of their photograph, as outlined in PLoS ONE consent form.).
Table 1.
Summary of Clinical Data for 20 Chinese WS2 Patients.
Figure 3.
Mutation analyses of Chinese WS2 families WS01, WS02, WS04, WS08, and WS09.
A. DNA sequence chromatograms showing heterozygous missense c.20A>G mutation identified in family WS02, compared with wild-type controls. The structure of MITF indicates the position of c.20A>G mutation in exon 1 and p. Y7C outside the HLH domain. B. DNA sequence chromatograms showing heterozygous missense c.332C>T mutation identified in family WS09, compared with wild-type controls. The structure of MITF indicates the position of c.332C>T mutation in exon 3 and p. A111V outside the HLH domain. C. DNA sequence chromatograms showing heterozygous c.647_649delGAA deletion mutation identified in family WS04, compared with wild-type controls. The structure of MITF indicates the position of c.647_649delGAA mutation in exon 7 and p. R217del in the HLH domain. D. DNA sequence chromatograms showing heterozygous missense c.649A>G mutation identified in family WS08, compared with wild-type controls. The structure of MITF indicates the position of c.649A>G mutation in exon 7 and p. R217G in the HLH domain. E. DNA sequence chromatograms showing heterozygous nonsense c.763C>T mutation identified in family WS01, compared with wild-type controls. The structure of MITF indicates the position of c.763C>T mutation in exon 8 and p. R255X in the HLH domain. F. Conservation analysis shows that the Arg residue at 217 in MITF is conserved across human, Pan troglodytes, macaca, canis, bos, Mus musculus, Rattus norvegicus, gallus, and Danio rerio. G. Schematic illustration of MITF gene structure showing the position of the mutations. AD1-3, transactivation domains; b, basic domain; HLH, helix-loop-helix domain; LZ, leucine zipper domain.
Table 2.
Summary of MITF Gene Mutations Identified in Chinese WS2 Patients.