A new locus for autosomal recessive spastic paraplegia associated with mental retardation and distal motor neuropathy, SPG14, maps to chromosome 3q27-q28.

Hereditary spastic paraplegias (HSPs), a group of neurodegenerative disorders that cause progressive spasticity of the lower limbs, are characterized by clinical and genetic heterogeneity. To date, three loci for autosomal recessive HSP have been mapped on chromosomes 8p, 16q, and 15q. After exclusion of linkage at these loci, we performed a genomewide search in a consanguineous Italian family with autosomal recessive HSP complicated by mild mental retardation and distal motor neuropathy. Using homozygosity mapping, we obtained positive LOD scores for markers on chromosome region 3q27-q28, with a maximum multipoint LOD score of 3.9 for marker D3S1601. Haplotype analysis allowed us to identify a homozygous region (4.5 cM), flanked by markers D3S1580 and D3S3669, that cosegregates with the disease. These data strongly support the presence, on chromosome 3q27-28, of a new locus for complicated recessive spastic paraplegia, which we have named "SPG14."

X-linked Charcot-Marie-Tooth disease. A linkage study in a large family by using 12 probes of the pericentromeric region.

Linkage analysis was performed on 41 subjects belonging to a large family with a recurrence of X-linked Charcot-Marie-Tooth disease (CMTX), by using 12 restriction fragment length polymorphism markers mapping in p11-q13. The results are in agreement with previous linkage data. Three new markers that are potentially useful for genetic analysis of CMTX families are described. A more precise estimate of the localization of the disease locus was attempted by multipoint linkage analysis.

Serum lipids, lipoprotein analysis and apoprotein A-I, A-II and B levels in Friedreich's ataxia.

Serum lipid, lipoprotein and apoprotein parameters were evaluated in 15 patients (7 males and 8 females) with Friedreich's ataxia. Serum lipid levels in patients showed no significant differences compared to controls. Small reduction in serum phospholipid and in total HDL and HDL3 cholesterol levels were observed, and the female patients presented a slight reduced total cholesterol level; among the serum apoproteins, apo B was reduced only in the males. The most interesting findings concerned the lipoproteins, since both lipid and protein masses of the VLDL, LDL and HDL2 fractions were reduced. In reference to lipoprotein composition, however, HDL2 was the most modified fraction, showing an important protein reduction. From this point of view, this lipoprotein seems the most responsible for the changes observed in our patients. The meaning of this modified lipoprotein pattern in the pathophysiology of Friedreich's ataxia is not clear.

Psychiatric disturbances associated with myasthenia gravis.

Seventy-four myasthenic patients (54 F, 20 M; mean age 49.6 years) were evaluated using the diagnostic criteria of the DSM-III in order to investigate the prevalence of psychiatric disturbances in this order. Fifty-one had had thymectomies, of whom 28 females had hyperplasia, two females and five males had involution of the thymus, and 10 females and six males had thymomata. Psychiatric disturbances were observed in 38 subjects (51%), in particular, adjustment disorders with depressed mood and mixed emotional features (19%) (22% including adjustment disorder with anxious mood), affective disorders (13.5%) and personality disorders (18%).

Correlation of ERG and pigment epithelium changes in external progressive ophthalmoplegia (EPO).

Six out of 17 patients with progressive external ophthalmoplegia (EPO) were found to have pigment anomalies with alterations in the electroretinographical (ERG) tracings. However, fluorangiography demonstrated alterations of the retinal pigment epithelium in patients with normal fundus and ERG examinations. We conclude that in our series there was no correlation between retinopathy and tapetoretinal degeneration.

Peroneal muscular atrophy with ataxia and partial myoclonic epilepsy.

Two brothers, 17 and 11 years old, presented with pes cavus, absence of deep tendon reflexes, péripheral vibratory sensory loss, ataxia, tremor, nystagmus, dysarthria and partial myoclonic epilepsy. Electromyography showed severe slowing of motor conduction velocity in the lower extremities and increased distal latencies. A peroneal nerve biopsy showed absence of myelin sheath in most fibres resulting in numerous demyelinated nerve fibres. The father and seven uncles on the paternal side had pes cavus, hammer toes and moderate vibratory peripheral sensory loss. Three of seven siblings had slow motor conduction velocities on EMG. None had EEG abnormalities. Epilepsy started at an early age in both patients with myoclonic jerks of the right arm especially during sleep. EEG recordings were characterized by focal or diffuse epileptiform discharges. In the elder brother a partial motor epileptic status occurred with adversive seizures involving the right side of the body. He died of a broncopneumonia after 3 days of this epileptic status. Histopathological examination showed a severe demyelination of dentato-rubral pathways in the cerebellum and a partial degeneration of Goll and Burdach's tracts in the cervical spinal cord. The nosological classification of this syndrome is discussed and an autosomal dominant inheritance with incomplete penetrance or variable expressivity is suggested.