ANAPC1 Mutations in Individuals with Rothmund-Thomson Syndrome Type 2
(A) Photos of three affected individuals show the alopecia and abnormal teeth, nails, and skin.
(B, top) Pedigrees of ten individuals from seven families with RTS type 1 and ANAPC1 mutations. All individuals affected have the ANAPC1 intronic splicing variant (GenBank: NM_022662.3:c.[2705−198C>T]). Individuals 1, 2, 3A, 3B, and 4 are homozygous for the ANAPC1 intronic splicing variant, whereas individuals 5, 6A, 6B, 7A, and 7B have compound-heterozygous mutations.
(B, bottom) Graphical representation of all ANAPC1 variants identified. Introns other than 22 are not drawn to scale. The domains of ANAPC1 are discussed in detail by Li et al. and Chang et al.24, 25 The WD40 domain mediates conformational changes important for stimulating the APC’s catalytic activity upon co-activator binding. The Mid-N and Mid-C domains coalesce together in the APC complex. The PC domain joins the APC platform to the tetratricopeptide repeat lobe of the APC.