Hereditary Spastic Paraplegia Linked to Abnormal Splicing From an AIMP1 Missense Variant.

Hereditary spastic paraplegias (HSP) are a diverse group of neurodegenerative diseases characterized by lower limb spasticity and weakness. To date, over 80 genes have been associated with HSP, but many families remain without a molecular diagnosis. In this study, linkage analysis and whole-exome sequencing (WES) were performed to identify the causal gene in a HSP family with autosomal recessive inheritance.

Anterior biopercular syndrome caused by unilateral infarction.

The anterior biopercular syndrome is characterized by facio-pharyngo-glosso-masticatory diplegia, with automatic dissociation of movements. It generally translates bilateral opercular lesion, often of vascular etiology. There are very few cases described with unilateral lesions.

PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4.

Asian origin for the worldwide-spread mutational event in Machado-Joseph disease.

Background: Machado-Joseph disease is the most frequent dominant ataxia worldwide. Despite its frequency and presence in many populations, only 2 founder mutations have been suggested to explain its current geographic distribution.

Objectives: To trace back in history the main mutational events in Machado-Joseph disease, we aimed to assess ancestral haplotypes and population backgrounds, to date the mutations, and to trace the routes and time of introduction of the founder haplotypes in different populations.

Molecular diagnosis of Huntington disease in Portugal: implications for genetic counselling and clinical practice.

Huntington disease (HD) is a neurodegenerative, autosomal dominant disorder of late-onset, caused by the expansion of a CAG repeat in the coding region of the gene. Ours is the reference laboratory for genetic testing in HD, in Portugal, since 1998; 90.1% of all 158 families known were identified for the first time, including patients with unusual presentation or without family history.