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P426L and I179S are the two most frequent mutations in juvenile and adult metachromatic leukodystrophy (late-onset MLD), which, in contrast to infantile MLD, show marked phenotypic heterogeneity.

To study the clinical and electrophysiologic features of a large series of carriers of the 17p11.2 deletion.

To relate X-linked Charcot-Marie-Tooth disease (CMTX) phenotypes to gender and type of neuropathy by the study of a large series of CMTX patients with proven Cx32 point mutations.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disease characterized by recurrent episodes of acute nerve palsies. We performed a clinical, electrophysiologic, and molecular study of 13 French families with HNPP associated with a chromosome 17∼11.2 deletion in 36 individuals. There were electrophysiologic abnormalities in all symptomatic (n = 28) and asymptomatic (n = 8) deletion carriers, even in childhood. Bilateral delayed distal motor latency of the median nerve at the wrist, reduced sensory velocity in the palm-wrist segment, and delayed distal motor latency or reduced motor velocity in the peroneal nerve was diagnostic in at-risk relatives. This large series confirms the reliability of molecular analysis combined with a simplified electrophysiologic examination for the diagnosis of HNPP associated with 17p11.2 deletion.

The authors report a family in which two affected first cousins had a severe demyelinating Charcot–Marie–Tooth disease (CMT) phenotype. One had related parents, and there were no other affected relatives, suggesting an autosomal recessive mode of inheritance. Molecular studies showed that a de novo duplication in 17p11.2 and a second mutation in MTMR2 were present.

Hereditary neuralgic amyotrophy (HNA) is an autosomal disease characterized by painful episodes of brachial palsy. The presence of tomacula in some patients suggested that HNA might be genetically related to hereditary neuropathy with liability to pressure palsies (HNPP), caused by point mutations in the PMP22gene or deletion of the region containing this gene. In a clinical, electrophysiologic, and molecular study of two families with HNA, we show that the PMP22gene is not deleted, duplicated, or mutated in HNA and that the disease is not linked to any other gene in the HNPP deleted region. We conclude that HNA and HNPP are distinct genetic entities.

Article abstract-We present clinical, neuropsychological, and neuropathologic data on a large pedigree including 34 subjects with early-onset progressive dementia. The mean (+\- SD) age at onset was 46 +\- 3.5 years and the mean age at death 52.6 +\- 5.7 years. Twelve patients were clinically diagnosed as having probable Alzheimer's disease (AD) according to the NINCDS-ADRDA criteria. Neuropsychological evaluation, performed at a moderate stage of the disease, was available in six subjects and showed a classic pattern of cognitive deficit. Myoclonus and extrapyramidal signs were common, and seizures were present in all affected subjects. There were neuropathologic changes typical of AD in two brains. A significant lod score of 5.48 was observed at a recombination fraction of theta = 0.0 with the genetic marker D14S43, thereby establishing that the responsible gene was located on chromosome 14q24.3. These results suggest that epilepsy could represent a particular feature in AD families linked to chromosome 14q.