title: Charcot-Marie-Tooth disease: a novel Tyr145Ser mutation in the myelin protein zero (MPZ, P0) gene causes different phenotypes in homozygous and heterozygous carriers within one family.
abstract: Charcot-Marie-Tooth disease type 1B (CMT 1B) is caused by mutations in the gene coding for peripheral myelin protein zero (MPZ, P0) that plays a fundamental role in adhesion and compaction of peripheral myelin. Here we report a Costa Rican family with a hereditary peripheral neuropathy due to a novel Tyr145Ser MPZ mutation. Four family members were heterozygously affected; two siblings of two heterozygous carriers were homozygous for this mutation. On neurological examination the heterozygous parents and their homozygous children both showed distal sensory deficits. The mother and the siblings displayed impaired deep tendon reflexes and mild sensory ataxia. The homozygous individuals were more severely affected with an earlier age of onset, distal motor weakness, and pupillary abnormalities. Electrophysiological studies revealed both signs of demyelination and axonal nerve degeneration. The sural nerve biopsy of one sibling showed thinly myelinated nerve fibers, onion bulb formation, and clusters of regenerating fibers. On electron microscopy axonal degeneration and decompaction of inner myelin layers were found. This Costa Rican family shows phenotypic variability depending on the homozygous or heterozygous state of the Tyr145Ser mutation carriers.
authors.affiliation: Institute of Health Research (INISA) and School of Biology, University of Costa Rica, San José, Costa Rica.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Leal
authors.forename: Corinna
authors.initials: C
authors.lastname: Berghoff
authors.forename: Martin
authors.initials: M
authors.lastname: Berghoff
authors.forename: Gerardo
authors.initials: G
authors.lastname: Del Valle
authors.forename: Carlos
authors.initials: C
authors.lastname: Contreras
authors.forename: Olga
authors.initials: O
authors.lastname: Montoya
authors.forename: Erick
authors.initials: E
authors.lastname: Hernández
authors.forename: Ramiro
authors.initials: R
authors.lastname: Barrantes
authors.forename: Ursula
authors.initials: U
authors.lastname: Schlötzer-Schrehardt
authors.forename: Bernhard
authors.initials: B
authors.lastname: Neundörfer
authors.forename: André
authors.initials: A
authors.lastname: Reis
authors.forename: Bernd
authors.initials: B
authors.lastname: Rautenstrauss
authors.forename: Dieter
authors.initials: D
authors.lastname: Heuss
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D003364:Costa Rica; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D018993:Myelin P0 Protein / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D013497:Sural Nerve / Q000473:pathology
chemical_list: D018993:Myelin P0 Protein