autosomal dominant neuropathies research - from Austria

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Abstract from Arch Neurol 2003 Mar;60(3):329-34

Autosomal dominant inherited neuropathies with prominent sensory loss

and mutilations: a review.

Auer-Grumbach M, De Jonghe P, Verhoeven K, Timmerman V, Wagner K,

Hartung HP, Nicholson GA.

Institute of Medical Biology and Human Genetics, Karl-Franzens

University Graz, Harrachgasse 21/8, A-8010 Graz, Austria.

Hereditary sensory neuropathies (HSNs) are rare disorders characterized

by progressive distal sensory loss, predominantly affecting the lower

limbs. Foot ulcers, severe skin and bone infections, arthropathy, and

amputations are frequent and feared complications. Occasionally,

patients complain of spontaneous shooting or lancinating pain. Autonomic

fibers can be affected to a variable degree. Patients with HSN can also

have severe distal weakness, and some HSN variants have therefore been

classified among the hereditary motor and sensory neuropathies (HMSNs).

Molecular genetic studies of autosomal dominant inherited neuropathies

with prominent sensory loss and ulceromutilating features have assigned

the genetic loci for HMSN type 2B (Charcot-Marie-Tooth syndrome type 2B)

and HSN type 1 to chromosomes 3q13-22 and

9q22.1-22.3, respectively. However, some families with HSN have been

excluded for linkage to these loci, suggesting further genetic

heterogeneity. Recently, disease-causing mutations in the SPTLC1 gene

have been identified in patients with HSN type 1. In this review, we

discuss the hallmark features associated with the distinct genetic

subtypes of autosomal dominant inherited HSN and provide

genotype-phenotype

correlations.