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J Child Neurol. 2015 Oct;30(11):1544-8. doi: 10.1177/0883073815571049. Epub 2015 Feb 18.

Complexity of the Hereditary Motor and Sensory Neuropathies: Clinical and Cellular Characterization of the MPZ p.D90E Mutation.

Author information

1
Centro de Investigación Príncipe Felipe (CIPF), CIPF associated unit to the IBV-CSIC, Valencia, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, CIBERER, Valencia, Spain.
2
Neuropediatrics Department, Hospital Universitario La Paz, Madrid, Spain.
3
Neuropathology Department, Hospital Universitario La Paz, Madrid, Spain.
4
Neuropediatrics Department, Hospital Universitario de Guadalajara, Guadalajara, Spain.
5
Centro de Investigación Príncipe Felipe (CIPF), CIPF associated unit to the IBV-CSIC, Valencia, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, CIBERER, Valencia, Spain Genetics Department, University of Valencia, Valencia, Spain cespinos@cipf.es.

Abstract

Early-onset hereditary motor and sensory neuropathies are rare diseases representing a broad clinical and genetic spectrum. Without a notable familial history, the clinical diagnosis is complicated because acquired causes of peripheral neuropathy, such as inflammatory neuropathies, neuropathies with toxic causes, and nutritional deficiencies, must be considered. We examined the clinical, electrophysiological, and pathologic manifestations of a boy with an initial diagnosis of chronic inflammatory demyelinating polyneuropathy. The progression of the disease despite treatment led to a suspicion of hereditary motor and sensory neuropathy. Genetic testing revealed the presence of the MPZ p.D90E mutation in heterozygosis. To clarify the pathogenicity of this mutation and achieve a conclusive diagnosis, we investigated the MPZ p.D90E mutation through in silico and cellular approaches. This study broadens the clinical phenotype of hereditary motor and sensory neuropathy due to MPZ mutation and emphasises the difficulty of achieving an accurate genetic diagnosis in a sporadic patient to provide an appropriate pharmacologic treatment.

KEYWORDS:

MPZ gene; aggregation assay; de novo mutation; hereditary motor and sensory neuropathy; inflammatory neuropathy

PMID:
25694466
DOI:
10.1177/0883073815571049
[Indexed for MEDLINE]

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