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BackgroundPhosphoribosyl pyrophosphate synthetase (PRS) I deficiency is a rare medical condition caused by missense mutations in PRPS1 that lead to three different phenotypes: Arts Syndrome (MIM 301835), X-linked Charcot-Marie-Tooth (CMTX5, MIM 311070) or X-linked non-syndromic sensorineural deafness (DFN2, MIM 304500). All three are X-linked recessively inherited and males affected display variable degree of central and peripheral neuropathy. We applied whole exome sequencing to a three-generation family with optic atrophy followed by retinitis pigmentosa (RP) in all three cases, and ataxia, progressive peripheral neuropathy and hearing loss with variable presentation.MethodsWhole exome sequencing was performed in two affecteds and one unaffected member of the family. Sanger sequencing was used to validate and segregate the 12 candidate mutations in the family and to confirm the absence of the novel variant in PRPS1 in 191 controls. The pathogenic role of the novel mutation in PRPS1 was assessed in silico and confirmed by enzymatic determination of PRS activity, mRNA expression and sequencing, and X-chromosome inactivation.ResultsA novel missense mutation was identified in PRPS1 in the affected females. Age of onset, presentation and severity of the phenotype are highly variable in the family: both the proband and her mother have neurological and ophthalmological symptoms, whereas the phenotype of the affected sister is milder and currently confined to the eye. Moreover, only the proband displayed a complete lack of expression of the wild type allele in leukocytes that seems to correlate with the degree of PRS deficiency and the severity of the phenotype. Interestingly, optic atrophy and RP are the only common manifestations to all three females and the only phenotype correlating with the degree of enzyme deficiency.ConclusionsThese results are in line with recent evidence of the existence of intermediate phenotypes in PRS-I deficiency syndromes and demonstrate that females can exhibit a disease phenotype as severe and complex as their male counterparts.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0190-9) contains supplementary material, which is available to authorized users.

The causes and mechanism behind motor complications in Parkinson disease (PD) are still a subject of debate. Several factors including age at onset, evolution in years, and initial medication can influence the onset and severity of motor complications in PD.We studied patients with recent diagnosis of PD who were followed up prospectively for 10 years. Analysis included the progression of these patients, as measured by the Unified Parkinson Disease Rating Scale scores and the presence of motor complications (motors fluctuations, dyskinesias, and gait freezing) over time. The patient group was studied as a whole and by subgroups classified according to age at onset, initial treatment, and sex.By the end of the first decade, most patients exhibited dyskinesias (91%), motor fluctuations (62%), and freezing of gait (68%). An association was found between several patients' characteristics and presence of motor complications by 5 years, though not after 10 years of follow up. The apparition of motor fluctuations was mainly related to initial treatment (odds ratio [OR], 3.87). The development of dyskinesias was linked to initial treatment (OR, 8.31), age at onset (OR, 0.90), and sex (OR, 12.87).

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