Figure 1.

The c.5425C>T change in NF1 is associated with a distinctive NF1 form. (a) Pedigrees of the three families cosegregting NF1 and the NF1 mutation. Squares and circles indicate males and females, respectively; open symbols indicate unaffected individuals, filled symbols indicate affected individuals; arrows indicate index cases, and symbols with a slash indicate deceased family members. WT, wild-type allele. (b) Representative clinical features of subjects heterozygous for the c.5425C>T missense change in NF1. This mutation is associated with a mild phenotype consisting mainly of pigmentary signs (CaLS and SF) and lack of NFs. Other typical findings, including LN, OPGs and osseous dysplasia are uncommon or absent, whereas a high incidence of facial features resembling NS is observed. (c) Location of Arg¹⁸⁰⁹ in the tridimensional structure of the neurofibromin Sec/PH-like bipartite module. The cartoon shows the ribbon representation of the module together with location of the residue (lateral chain reported as stick representation) mutated in the studied NF1 subjects. The Sec domain (residues 1560–1698) (pink), which is implicated in lipid binding, is connected to a regulatory PH-like domain (residues 1715–1816) (light blue) by a partly helical linker (residues 1699–1714) (yellow). Arg¹⁸⁰⁹ (red) is in close contact with the backbone of Ser¹⁷³⁸ (dark blue). The H-bond between these residues is also shown (black line).