Comparative diagnosis interest of NfL and pNfH in CSF and plasma in a context of FTD-ALS spectrum.

Objective: The 'Frontotemporal dementia-Amyotrophic lateral sclerosis Spectrum' (FAS) encompasses different phenotypes, including cognitive disorders (frontotemporal dementia, FTD) and/or motor impairments (amyotrophic lateral sclerosis, ALS). The aim of this study was to apprehend the specific uses of neurofilaments light chain (NfL) and phosphorylated neurofilaments heavy chain (pNfH) in a context of FAS.

Methods: First, NfL and pNfH were measured in 39 paired cerebrospinal fluid (CSF) and plasma samples of FAS and primary psychiatric disorders (PPD) patients, considered as controls.

Predictive testing for Huntington disease over 24 years: Evolution of the profile of the participants and analysis of symptoms.

Background: Huntington disease (HD) is a devastating neurodegenerative autosomal dominant genetic condition. Predictive testing (PT) is available through a defined protocol for at-risk individuals. We analyzed the over-24-years evolution of practices regarding PT for HD in a single center.

Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with .

Objective: We took advantage of a large multinational recruitment to delineate genotype-phenotype correlations in a large, trans-European multicenter cohort of patients with spastic paraplegia gene 7 ().

Methods: We analyzed clinical and genetic data from 241 patients with , integrating neurologic follow-up data. One case was examined neuropathologically.

Efficacy of Exome-Targeted Capture Sequencing to Detect Mutations in Known Cerebellar Ataxia Genes.

Importance: Molecular diagnosis is difficult to achieve in disease groups with a highly heterogeneous genetic background, such as cerebellar ataxia (CA). In many patients, candidate gene sequencing or focused resequencing arrays do not allow investigators to reach a genetic conclusion.

Objectives: To assess the efficacy of exome-targeted capture sequencing to detect mutations in genes broadly linked to CA in a large cohort of undiagnosed patients and to investigate their prevalence.

Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues.

X-linked myotubular myopathy (XLMTM), a severe congenital myopathy, is caused by mutations in the MTM1 gene located on the X chromosome. A majority of affected males die in the early postnatal period, whereas female carriers are believed to be usually asymptomatic. Nevertheless, several affected females have been reported.

Congenital hypomyelinating neuropathy due to the association of a truncating mutation in PMP22 with the classical HNPP deletion.

Congenital hypomyelinating neuropathy appears early in life, resulting in a delay of motor and sensory development. Mutations involve genes such as myelin protein zero (MPZ), peripheral myelin protein 22 (PMP22), and early growth response 2 (EGR2). We present a patient with two compound mutations in PMP22: a point mutation causing a premature STOP codon in exon 3 was inherited from the mother on the first allele, and the "typical" PMP22 deletion in the 17p11.

Motor and respiratory heterogeneity in Duchenne patients: implication for clinical trials.

Aims: Our objective was to clarify the clinical heterogeneity in Duchenne muscular dystrophy (DMD).

Methods: The French dystrophinopathy database provided clinical, histochemical and molecular data of 278 DMD patients (mean longitudinal follow-up: 14.2 years).

REEP1 mutations in SPG31: frequency, mutational spectrum, and potential association with mitochondrial morpho-functional dysfunction.

Hereditary spastic paraplegias (HSP) constitute a heterogeneous group of neurodegenerative disorders characterized at least by slowly progressive spasticity of the lower limbs. Mutations in REEP1 were recently associated with a pure dominant HSP, SPG31. We sequenced all exons of REEP1 and searched for rearrangements by multiplex ligation-dependent probe amplification (MLPA) in a large panel of 175 unrelated HSP index patients from kindreds with dominant inheritance (AD-HSP), with either pure (n = 102) or complicated (n = 73) forms of the disease, after exclusion of other known HSP genes.

Spinocerebellar ataxia type 11 (SCA11) is an uncommon cause of dominant ataxia among French and German kindreds.

Background: At least 28 loci have been linked to autosomal dominant spinocerebellar ataxia (ADCA). Causative genes have been cloned for 10 nucleotide repeat expansions (SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and 31) and six genes with classical mutations (SCA5, 13, 14, 15/16, 27 and 28). Recently, a large British pedigree linked to SCA11 has been reported to carry a mutation in the TTBK2 gene.

Analysis of the DYSF mutational spectrum in a large cohort of patients.

Dysferlinopathies belong to the heterogeneous group of autosomal recessive muscular dystrophies. Mutations in the gene encoding dysferlin (DYSF) lead to distinct phenotypes, mainly Limb Girdle Muscular Dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM). Here, we analysed the mutational data from the largest cohort described to date, a cohort of 134 patients, included based on clinical suspicion of primary dysferlinopathy and/or dysferlin protein deficiency identified on muscle biopsy samples.

Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis.

Autosomal recessive renal tubular dysgenesis is a severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (Potter phenotype). Absence or paucity of differentiated proximal tubules is the histopathological hallmark of the disease and may be associated with skull ossification defects. We studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1.

Mutation in the catalytic domain of protein kinase C gamma and extension of the phenotype associated with spinocerebellar ataxia type 14.

Background: Autosomal dominant cerebellar ataxias comprise a clinically, neuropathologically, and genetically heterogeneous group of neurodegenerative disorders. The vast majority of cases are caused by trinucleotide or pentanucleotide repeat expansions in 9 different genes. Spinocerebellar ataxia type 14 (SCA14) is a relatively pure form of autosomal dominant cerebellar ataxia mapped to chromosome 19q and caused by missense mutations in the gene encoding protein kinase C gamma (PRKCG), which are all located in the regulatory domain.