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Friedreich's ataxia (FRDA) is caused by homozygous GAA repeat expansions or compound heterozygous (CH) mutations in FXN gene. Its broad clinical spectrum makes it difficult to identify, thus an accurate diagnosis can only be made by genetic testing.This study aims to present data on FXN variants observed in patients with sporadic or recessive ataxia, including detailed data of the first CH Mexican patients.One hundred and eight patients with recessive or sporadic cerebellar ataxia were referred to our institution between 2009 and 2019 for FXN molecular testing. This was achieved using a combined methodology of triplet repeat-primed PCR (polymerase chain reaction), long PCR, FXN sequencing and multiplex-ligation probe-amplification.Eighteen patients had a homozygous FXN genotype; whereas five were CH patients with a slow progression and phenotypic variability, including a late-onset case with spastic paraparesis, and a Charcot-Marie-Tooth-like case.These first Mexican CH patients pose important implications for genetic counseling and FRDA management.

Clozapine (CLZ) is an atypical antipsychotic and the gold standard for refractory psychosis treatment. However, there is little information regarding pharmacogenetics of CLZ in patients with refractory psychosis and its clinical correlation with alcohol intake. Although neurological effects of CLZ in patients with concomitant alcohol intake are documented, its use is very common in patients with psychosis. We explored the impact of CYP1A2, CYP2D6, CYP2C19, and CYP3A4 genetic variants on CLZ pharmacokinetics and side effects, along with coffee/alcohol/tobacco consumption habits and clinical data of 48 adult patients with refractory psychosis on CLZ antipsychotic monotherapy. Relevant CYP variants in CLZ metabolism were evaluated by targeted genotyping and multiplex ligation-dependent probe amplification. CLZ and its main metabolite plasma concentrations were determined by high performance liquid chromatography. Biochemical and molecular data, along with other potential confounders, were included in the analysis by linear regression. Overall, CYP variants showed no effect on CLZ pharmacokinetics. The rs2069514 variant in homozygous genotype (also known as CYP1A2*1C/*1C) was associated with CLZ adverse reactions in Mexican patients with refractory psychosis (OR = 3.55 CI95 = 1.041-12.269, p = .043) and demonstrated that this effect is doubled by concomitant alcohol consumption (OR = 7.9 CI95 = 1.473-42.369, p = .016). Clinicians should be aware of this information before starting CLZ use, when treating patients with refractory psychosis, who are alcohol drinkers and carriers of this genetic variant in order to prevent CLZ-related adverse reactions. Nevertheless, our findings should be replicated in larger samples.