Neurogenetics
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Mutations in the LRRK2 gene are a cause of autosomal dominant Parkinson's disease (PD). Whether LRRK2 variants influence susceptibility to the commoner, sporadic forms of PD remains largely unknown. Data are particularly limited concerning the Asian population. ⋯ Two novel variants, Met1869Val and Glu1874Stop, were found in one PD case each; their pathogenic role remains, therefore, uncertain. The remaining two novel variants (Ala419Val and Pro755Leu) were present with similar frequency in cases and controls, and were therefore, interpreted as disease-unrelated polymorphisms. Our findings suggest that the LRRK2 Gly2385Arg is the first identified, functionally relevant variant, which acts as common risk factor for sporadic PD in the population of Chinese ethnicity.
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Dystrophin deficiency leads to the progressive muscle wasting disease Duchenne muscular dystrophy (DMD). Dystrophin-deficient mdx mice are characterized by skeletal muscle weakness and degeneration but they appear outwardly normal in contrast to DMD patients. Mice lacking both dystrophin and the dystrophin homolog utrophin [double knockout (dko)] have muscle degeneration similar to mdx mice, but they display clinical features similar to DMD patients. ⋯ To investigate whether any upregulation of slow genes is retained in vitro, independent of postsynaptic membrane abnormalities, we derived mdx and dko primary myogenic cultures and analyzed the expression of Myh7 and Myl2. Real-time reverse transcriptase-polymerase chain reaction analysis demonstrates that transcription of these slow genes is also upregulated in dko vs mdx myotubes. This data suggests that at least part of the fiber-type abnormality is due directly to the combined absence of utrophin and dystrophin and is not an indirect effect of the postsynaptic membrane abnormalities.
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Familial hemiplegic migraine (FHM), a rare autosomal dominant subtype of migraine with aura, has been linked to two chromosomal loci, 19p13 and 1q23. Mutations in the Na+K+-ATPase alpha2 subunit gene, ATP1A2, on 1q23 have recently been shown to cause familial hemiplegic migraine type 2 (FHM2). We sequenced the coding regions of this gene in a Finnish chromosome 1q23-linked FHM family with associated symptoms such as coma and identified a novel A1033G mutation in exon 9. ⋯ This residue is located in a highly conserved N-terminal region of the M4-5 loop of the Na+,K+-ATPase. Furthermore, the T345A mutation co-segregated with the disorder in our family and was not present in 132 healthy Finnish control individuals. For these reasons it is most likely the FHM-causing mutation in this family.