Abstract
We compared 25 autosomal dominant hereditary motor and sensory neuropathy (HMSN) type I patients with 7 subjects affected by hypertrophic HMSN with non-dominant inheritance. All the autosomal dominant HMSN I cases carried the chromosome 17p11.2 duplication, providing evidence that it is widely represented in HMSN I families. The second group included: Two siblings born to unrelated, unaffected parents and suffering from hypertrophic HMSN of strikingly different severity; two sisters with HMSN I phenotype, born to first-cousin unaffected parents; two brothers with HMSN III phenotype born to unrelated parents both showing HMSN II phenotype; a child with classic HMSN III phenotype, born to unrelated, unaffected parents. The 17p11.2 duplication was not found in any of the patients of the second series or in their parents. Our data provide further evidence that: HMSN III is heterogeneous and encompasses the homozygous expressions of different neuropathic genes; it is advisable to separate autosomal recessive hypertrophic HMSN from dominant HMSN Ia, because they appear to be due to different DNA mutations.
Sommario
Abbiamo paragonato 25 pazienti affetti da neuropatia ereditaria sensitivo-motoria (HMSN) di tipo I ad ereditarietà autosomica dominante con 7 pazienti affetti da neuropatia ipertrofica ad ereditarietà non dominante. Tutti i pazienti con ereditarietà autosomica dominante sono risultati portatori della duplicazione 17p11.2, dimostrando così che questa è largamente presente nelle famiglie HMSN I. Il secondo gruppo comprendeva: due fratelli affetti da una neuropatia ipertrofica di gravità nettamente diversa, nati da genitori sani non consanguinei; due sorelle con un fenotipo HMSN I nate da genitori sani, cugini di primo grado; due fratelli con un fenotipo HMSN III nati da genitori non consanguinei affetti da HMSN II; un bimbo con un classico fenotipo HMSN III, nato da genitori sani, non consanguinei. L'analisi del DNA ha dimostrato l'assenza della duplicazione sia nei pazienti del secondo gruppo che nei loro genitori. I nostri dati dimostrano che: l'HMSN III è eterogenea e comprende pazienti omozigoti per differenti geni neuropatogeni; è opportuno tenere distinti i pazienti con neuropatia ipertrofica recessiva da quelli portatori di una HMSN Ia dominante poiché è probabile che le due malattie siano dovute a difetti genici diversi.
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DNA analyses were supported by grants from P.F. Biotecnologie CNR, Telethon, Murst 40% and 60%.
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Sghirlanzoni, A., Pareyson, D., Marazzi, R. et al. Homozygous hypertrophic hereditary motor and sensory neuropathies. Ital J Neuro Sci 15, 5–14 (1994). https://doi.org/10.1007/BF02343492
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DOI: https://doi.org/10.1007/BF02343492