Figure 1. Deletions and mutations in PUM1 identified in early- and late-onset diseases.

(A) Deletions spanning PUM1 on chromosome 1p35.2 (shown in red) were identified in nine patients with developmental disability; Mb, megabases. Dashed lines indicate the minimal region spanning PUM1. (B) Schematic of the PUM1 protein. Low-complexity regions are shown as purple boxes and PUM1 homology domains (HDs) as orange boxes. Locations of the PUM1 mutations in subjects 10, 11 and Family X are indicated. (C) Pedigree shows autosomal dominant inheritance of adult-onset ataxia in Family X. White and black denote unaffected and affected individuals, respectively; squares indicate males and circles indicate females; diamonds and numbers indicate the respective offspring; a line through the box indicates the individual is deceased. Subjects 12–18, who have been sequenced, are numbered in the order in which they were identified; DNA was not available from affected individuals without a subject number. S17 (asterisk) carries the familial mutation but does not have reported ataxia. The square box with dots (the great-grandfather of the proband) is a deceased individual who began using a walker in his 30s or 40s. The red arrow indicates the proband (Subject 12). (D) Protein alignment and comparison of the affected PUM1 residues compared to 21 organisms from human to Drosophila melanogaster. Different colors highlight degree of conservation: yellow for full conservation, light blue if conserved in all but one organism, and gray if more than one organism does not share the same amino acid. The human PUM1 amino acid sequence is used here as the reference protein. See also Figure S1 and Table S1, S2 and S3.