20 research outputs found
A 71-nucleotide deletion in the periaxin gene in an Italian patient with late-onset slowly progressive demyelinating CMT
Background: Charcot-Marie-Tooth disease (CMT) constitutes a group of heterogeneous hereditary motor and sensor neuropathies. Mutations in the periaxin (PRX) gene cause CMT4F with an autosomal recessive early-onset demyelinating neuropathy and are extremely rare in a non-Romani white population. Methods: We report on a 66-year-old Italian man presenting with slowly progressive and late-onset demyelinating CMT. The molecular analysis was performed using a custom panel containing 39 genes associated with the CMT phenotype. Results: The patient harbored a homozygous PRX 71-nucleotide deletion (c.3286_3356del71, I1096fsX17). Conclusions: This is the first report that describes such a genetic mutation in a population of non-Romani origin
FUS MUTATIONS IN SPORADIC AMYOTROPHIC LATERAL SCLEROSIS: CLINICAL AND GENETIC ANALYSIS
Fused in sarcoma (FUS) or translocation in liposarcoma (TLS), a DNA/RNA-binding protein, causes a dominant autosomal inherited form
of amyotrophic lateral sclerosis (ALS), ALS 6. Its main role in neurodegeneration is highlighted by the presence of cytoplasmic
accumulation of its mutant protein form in ALS patients. To further define the frequency and spectrum of FUS gene mutations, we have
performed a molecular screening of a cohort of 327 Italian patients from Southern Italy with sporadic ALS (SALS). We identified 4 patients
carrying 3 different missense mutations and several polymorphisms. Two different substitutions occurring in the same amino acidic position
have been observed in 2 patients: R521G and R521C respectively; P525L mutation has been found in 2 additional cases. Most of the patients
with FUS mutations showed early symptom onset and had short disease survival. We also detected 4 different polymorphic variants
(3=-untranslated region [UTR] variant, c.*41G.A; c.52313ins[GAGGTG]; c.335-15del[TTTT]; and rs13331793) in 9 patients from within
our cohort. This study underlines the importance of population-based mutation screening of newly identified genes.
\ua9 2011 Elsevier Inc. All rights reserved
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Exome sequencing reveals two FA2H mutations in a family with a complicated form of Hereditary Spastic Paraplegia and psychiatric impairments
Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia
Mutations in the SPG4 gene are the most common causes of hereditary spastic paraplegia (HSP) accounting for up to 40% of autosomal dominant (AD) forms and 12-18% of sporadic cases. The phenotype associated with HSP due to mutations in the SPG4 gene tends to be pure. There is increasing evidence, however, of patients with complicated forms of spastic paraplegia in which SPG4 mutations were identified. A cohort of 38 unrelated Italian patients with spastic paraplegia, of which 24 had a clear dominant inheritance and 14 were apparently sporadic, were screened for mutations in the SPG4 gene. We identified 11 different mutations, six of which were novel (p.Glu143GlyfsX8, p.Tyr415X, p.Asp548Asn, c.1656_1664delinsTGACCT, c.1688-3C>G and c.*2G>T) and two exon deletions previously reported. The overall rate of SPG4 gene mutation in our patients was 36.8% (14/38); in AD-HSP we observed a mutation frequency of 45.8% (11/24), in sporadic cases the frequency was 21.4% (3/14). Furthermore, we found a mutational rate of 22.2% (2/9) and 41.4% (12/29) in the complicated and pure forms, respectively. The results underlie the importance of genetic testing in all affected individuals