The fragile X syndrome (FRAXA) is the most widespread heritable form of mental retardation caused by the lack of expression of the fragile X mental retardation protein (FMRP). This lack has been related to deficits in cerebellum-mediated acquisition of conditioned eyelid responses in individuals with FRAXA. In the present behavioral study, long-term effects of deficiency of FMRP were investigated by examining the acquisition, savings and extinction of delay eyeblink conditioning in male individuals with FRAXA. In the acquisition experiment, subjects with FRAXA displayed a significantly poor performance compared with controls. In the savings experiment performed at least 6 months later, subjects with FRAXA and controls showed similar levels of savings of conditioned responses. Subsequently, extinction was faster in subjects with FRAXA than in controls. These findings confirm that absence of the FMRP affects cerebellar motor learning. The normal performance in the savings experiment and aberrant performance in the acquisition and extinction experiments of individuals with FRAXA suggest that different mechanisms underlie acquisition, savings and extinction of cerebellar motor learning.

Fragile X (FRAX) syndrome is a commonly inherited form of mental retardation resulting from the lack of expression of the fragile X mental retardation protein (FMRP). It is caused by a stretch of CGG repeats within the fragile X gene, which can be unstable in length as it is transmitted from generation to generation. Once the repeat exceeds a threshold length, the FMR1 gene is methylated and no protein is produced resulting in the fragile X phenotype. The consequences of FMRP absence in the mechanisms underlying mental retardation are unknown. We have identified a male patient in a classical FRAX family without the characteristic FRAX phenotype. His intelligence quotient (IQ) is borderline normal despite the presence of a mosaic pattern of a pre‐mutation (25%), full mutation (60%) and a deletion (15%) in the FMR1 gene. The cognitive performance was determined at the age of 28 by the Raven test and his IQ was 81. However, FMRP expression studies in both hair roots and lymphocytes, determined at the same time as the IQ test, were within the affected male range. The percentage of conditioned responses after delay eyeblink conditioning was much higher than the average percentage measured in FRAX studies. Moreover, this patient showed no correlation between FMRP expression and phenotype and no correlation between DNA diagnostics and phenotype.

Absence of functional FMRP causes Fragile X syndrome. Abnormalities in synaptic processes in the cerebral cortex and hippocampus contribute to cognitive deficits in Fragile X patients. So far, the potential roles of cerebellar deficits have not been investigated. Here, we demonstrate that both global and Purkinje cell-specific knockouts of Fmr1 show deficits in classical delay eye-blink conditioning in that the percentage of conditioned responses as well as their peak amplitude and peak velocity are reduced. Purkinje cells of these mice show elongated spines and enhanced LTD induction at the parallel fiber synapses that innervate these spines. Moreover, Fragile X patients display the same cerebellar deficits in eye-blink conditioning as the mutant mice. These data indicate that a lack of FMRP leads to cerebellar deficits at both the cellular and behavioral levels and raise the possibility that cerebellar dysfunctions can contribute to motor learning deficits in Fragile X patients.

Neuroanatomical tract-tracing methods were used to study the topography of the reticulocollicular projections. Injections of gold-HRP or BDA tracers into the medial and/or central portions of the superior colliculus resulted in labelled neurones mainly in the medial reticular formation, whereas injections into the lateral portion of the superior colliculus showed labelling in the medial and lateral reticular formation. When tracer was injected into the lateral portion of the caudal superior colliculus, extensive lateral labelling was observed in the contralateral parvocellular reticular nucleus and the contralateral dorsal medullary reticular nucleus, two areas involved in reflex blinking. The present study shows that these reticular areas project to the lateral superior colliculus, which is known to be involved in the coordination of eye and eyelid movements.

Mseleni Joint Disease (MJD), a polyarticular osteoarthritis of uncertain etiology is endemic among the Tonga-Zulu tribe. The traditional diet is deficient in calcium, and palm wine (2–4% alcohol) is drunk widely. Patients with MJD are reported to be more osteopenic than those without. Iliac bone biopsies of 19 arthritic patients were examined by routine histomorphometry and revealed decreased trabecular bone volume (p < 0.0005), increased resorption surfaces (p < 0.01), decreased bone formation rate at the BMU (p < 0.01) level and increased mineralization lag time (p < 0.01). Six of the 19 patients (31.6%) had features of osteomalacia and six (31.6%) signs of osteoblast failure. The most likely cause of the bone disorder is calcium deficiency, but inanition, inactivity and alcohol abuse may have contributed. Although the joint disorder may have contributed to the bone disorder, the converse is unlikely the case.

A study to measure the prevalence of motor disability and impairment using an interview survey and a follow-up medical examination has been carried out in a rural area in KwaZulu, South Africa. A 10% random cluster sample yielded 1659 individuals of all ages. One hundred and forty-three were reported to have motor disability, giving a crude motor disability rate of 86/1000. One hundred and twenty-six were followed up and 86 had demonstrable impairment, giving a crude motor impairment rate of 52/1000. The commonest impairment was osteoarthritis of the hips (20/1000) which may be the same disease as has been reported in neighbouring areas and to which the name Mseleni joint disease (MJD) has been applied.