Figure 1: SLC39A14 mutations lead to cerebral Mn deposition associated with characteristic MRI brain appearances.
From: Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism–dystonia
(a) Schematic of SLC39A14 showing its eight TMDs (pink and blue cylinders) interlinked by intracellular and extracellular loops35. TMD II, III, IV and VII (pink) are postulated by the transmembrane protein topology prediction tool MemSatSVM (see URLs) to form a pore. The histidine-rich (HXHXHX) and metalloprotease motif (EEXPHEXGD) are highlighted in orange. Mutated amino-acid residues are indicated by red circles. (b) Pedigrees and sequence chromatograms of family A-E. Affected individuals are indicated by black shading. Squares represent males, circles females and a double line a consanguineous union. Mutated bases are boxed in black. For each family, the top chromatogram shows the wild-type SLC39A14 sequence and the hromatogram below the homozygous SLC39A14 mutation identified in the affected individuals. Parental studies for families A, B, C and E demonstrate that both parents are heterozygous carriers of the identified mutation. (c) Representative MRI brain images of patients with SLC39A14 mutations showing characteristic radiological features: individual C-II-2 aged 3 years and E-II-2 aged 17 years. Generalized T1-hyperintensity of the cerebral white matter, globus pallidus (yellow arrows) and striatum (blue arrows), pituitary gland (white arrows), dorsal pons (pink arrows) and cerebellum (turquoise arrows) can be observed. Hypointensity of the globus pallidus is also evident on T2 and T2*-weighted imaging (white dashed arrows).
