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OBJECTIVE To determine clinical features and to identify changes in brain structure and function in compound heterozygous and heterozygous ATP13A2 mutation carriers. DESIGN Prospective multimodal clinical and neuroimaging study. SETTING University of Lübeck, Lübeck, Germany. PARTICIPANTS Eight family members of a large Chilean pedigree with Kufor-Rakeb syndrome (KRS). INTERVENTIONS Clinical characterization, dopamine transporter (DAT) imaging, voxel-based morphometry (VBM), and transcranial sonography (TCS). MAIN OUTCOME MEASURES Frequency of parkinsonian signs, brain structure, and functional alterations. RESULTS The only available patient with compound heterozygous KRS showed a markedly reduced striatal DAT density bilaterally. Magnetic resonance imaging revealed severe global brain atrophy as well as iron deposition in the basal ganglia. The heterozygous mother had definite parkinsonism with reduced DAT density in both putamina. While all asymptomatic heterozygous siblings displayed subtle extrapyramidal signs, DAT imaging revealed striatal tracer uptake within physiological levels. Voxel-based morphometry revealed an increase in gray matter volume in the right putamen and a decrease in the cerebellum of the heterozygous carriers. In all mutation carriers, the substantia nigra had a normal appearance on TCS. CONCLUSIONS Single ATP13A2 heterozygous mutations may be associated with clinical signs of parkinsonism and contribute to structural and functional brain changes. Lack of hyperechogenicity in the substantia nigra may be a distinctive feature of this form of genetic parkinsonism. This, along with the finding of iron in the basal ganglia in our patient with KRS, implies a different underlying pathophysiology compared with other monogenic forms of parkinsonism and idiopathic PD and may place KRS among the syndromes of neurodegeneration with brain iron accumulation (NBIA).Arch Neurol. 2010;67(11):1357-1363--

Restless legs syndrome (RLS) is a common sensory-motor disorder characterized by paresthesias and an intense urge to move the legs with a considerable familial aggregation. To date, no gene mutation has been found, but five gene loci have been mapped in primary RLS to chromosomes 12q, 14q, 9p, 2q, and 20p (RLS1 through 5).

BACKGROUND Although homozygous mutations in the PTEN-induced putative kinase 1 (PINK1) gene have been unequivocally associated with early-onset Parkinson disease (PD), the role of single heterozygous PINK1 mutations is less clear. OBJECTIVE To investigate the role of homozygous and heterozygous PINK1 mutations in a large German pedigree (family W). DESIGN Mutation analysis of PINK1 and results of standardized neurological and motor examination by 3 independent movement disorder specialists, including blinded video rating. SETTINGS University of Lübeck. PARTICIPANTS Twenty family members. MAIN OUTCOME MEASURES The PINK1 genotype and PD status of all family members. RESULTS The index patient of family W carried a homozygous nonsense mutation (c.1366C>T; p.Q456X) and presented with a phenotype closely resembling idiopathic PD but with an onset at 39 years of age. The family included a total of 4 affected homozygous members (age, 60-71 years; age at onset, 39-61 years), 6 members with slight or mild signs of PD (affected) and a heterozygous mutation (age, 31-49 years), and 5 unaffected heterozygous mutation carriers (age, 34-44 years). Although none of the heterozygous affected family members was aware of their signs (asymptomatic), the clinical findings were unequivocal and predominantly or exclusively present on their dominant right-hand side, eg, unilaterally reduced or absent arm swing and unilateral rigidity. The heterozygous members were all considerably younger than the affected homozygous mutation carriers. CONCLUSIONS Heterozygous PINK1 mutations may predispose to PD, as was previously suggested by the presence of dopamine hypometabolism in asymptomatic mutation carriers. Long-term follow-up of our large family W provides an excellent opportunity to further evaluate the role of single heterozygous PINK1 mutations later in life, which will have major implications on genetic counseling.Arch Neurol. 2006;63:833-838 --

Mutations in the Parkingene (PARK2) are the most commonly identified cause of recessively inherited early-onset Parkinson disease (EOPD) but account for only a portion of cases. DJ-1(PARK7) was recently reported as a second gene associated with recessively inherited PD with a homozygous exon deletion and a homozygous point mutation in two families.

The ethanolic extract of sage(Salvia officinalisL.) was separated into five fractions through reextraction with supercritical CO2. Further fractionation of the most active antioxidant fractions by means of liquid chromatography, with silicic acid as absorbent, yielded 2H-10,4a-(epoxy methano)-phenantren-12-one-1,3,4,9,10,10ahexahydro-5, 6-dihydroxy-9a-ethoxy-1,1-dimethyl-7-(1methylethy), (rosmanol-9-ethyl ether). The same compound was isolated from the alcoholic extract of the hyssop(Hyssopus officinalisL.). Rosmanol-9-ethyl ether was shown to be one of the active antioxidant components in sage and hyssop, with activity much greater than butylated hydroxytoluene (BHT).

The title compound: 2H-10,4a-(epoxy-methano)-phenantren-12-one-1,3,4,9,10,10a-hexahydro-5,6-dihydroxy-9a-etoxy-1,1-dirnethyl-7-(1-methylethyl), was isolated fromSalvia officinalis L. andHyssopus officinalis L. C22H30O5, orthorhombic, P212121, (No. 19)a=8.309(1),b=11.320(2),c=22.060(3) Å,V=2075.0(9) Å3,Z=4,Dx=1.199 g·cm-3, ?(CuKa)=1.54184 Å,µ=6.43 cm-1, F(000)=808,T=296(1) K. The structure was solved by direct methods and refined toR=0.047 for 1824 observed reflections collected on a CAD-4 diffractometer. In the course of structure refinement conformational disorder of the isopropyl moiety and the terminal methyl group pertaining to the ethoxy ligand was established. They result altogether in four different conformers.

The title compound 2H-10,4a-(epoxy-methano)-phenantren-12-one-l,3,4,9,10,10a-hexahydro-6-hydroxy-5-methoxy-9-keto-1,1-dimethyl-7-(1-methylethyl) isolated fromSalvia officinalis L. have been investigated by nuclear magnetic resonance (NMR) spectroscopy and X-ray analysis. Investigation of1H and13C NMR, homonuclear (COSY) (1H-1H) and heteronuclear (1H-13C) spectra, permitted the unambiguous assignment of the1H and13C spectra, what gave the possibility to resolve the signals of similar natural products. Crystal data are: C21H26O5,Mr=358.43, orthorhombic,P21,21,21, (No. 19),a=10.671(2),b=11.976(3),c=14.601(5)Å,V=1865.9(9)Å3,Z=4,Dx=1.276 mg-3, ?(MoKa)=0.7107 Å,µ=0.84 cm-1, F(000)=768,T=293(1) K. The structure was solved by direct methods and refined toR=0.041 for 1832 observed reflections collected on CAD-4 diffractometer.

Usnic acid, 1,3(2H,9bH)-dibenzofurandione-2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyl, (1) was isolated from the lichenUsnea barbata by supercritical CO2 extraction. The corresponding sodium salt 2 1/2 hydrate was obtained by reacting the acid with sodium carbonate. (C18H15O7Na·2.5 H2O) × 2,Mr=822.68, triclinic,P1,a=14.179(8),b=7.369(4),c=9.109(6)Å,a=88.47(2),ß=105.35(2),?=92.27(2)°,V=917(2)Å3,Z=1,Dx=1.490 g cm-3, ?(MoKa)=0.71073 Å,µ=1.32 cm-1,F(000)=430,T=293(2)K. The structure was solved by direct methods and refined toR=0.038 for 3229 observed reflections. Both Na ions are pentacoordinated. Their coordination polyhedra are distorted square pyramids bound together by a common water molecule (OW1). The molecules are also joined together by a common water oxygen (OW2) in an infinite chain which lies parallel to theb-axis. The chains are held together by hydrogen bonds. The conformation of usnic acid in the complex differs from that found previously by a rotation of the acetyl group bound to the cyclohexadienone ring.

The electrochemical behaviour and mechanism of the redox process of the natural antioxidant rosmanol 9-ethyl ether, isolated fromSaliva officinalis L., were studied. The cyclic voltammograms of rosmanol 9-ethyl ether (R9EE), at characteristic pH values, and the electrochemical parameters for all investigated pH values were measured. Three characteristic pH regions, each with different behaviour of R9EE, were identified. In regions of pH < 4 and pH > 5 only one anodic peak appeared, whereas in the solutions of pH 4–5 two anodic peaks could be noted. The overall oxidation mechanism at pH < 4 is an e.H.e.H. oxidation mechanism, which as a final product gives a quinonic molecule. The influence of pH on the second oxidation peak potential tends towards zero in accordance with the preceding dissociation of the one of phenolic groups, thus suggesting an e.e.H. mechanism at pH > 5. This means that at the pH values expected in plant cells, R9EE has an unexpected structure, making this substance a potent antioxidant. Electrochemical and spectrophotometric measurements enabled us to establish an extremely low pKa value (4.35) for R9EE.