Compound Charcot-Marie-Tooth disease may determine unusual and milder phenotypes.
Compound forms of Charcot-Marie-Tooth (CMT) disease have been recently associated with unusually severe neuropathies, an observation that prompted the proposition that the additive effects of two mutations should be searched in patients whose clinical severity falls outside the common CMT phenotypes. In this report, we present a father and a daughter with a very mild and unusual disease that segregates with two mutations in PMP22 gene, the 17p11.2-p12 duplication and a Ser72Leu point mutation. We propose that the deleterious effects of each mutation are partially compensated by the functional effect of the other.
Gouvea
Silmara P
SP
Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
S Borghetti
Vinícius H
VH
Bueno
Keity C
KC
Genari
Adriana B
AB
Lourenço
Charles M
CM
Sobreira
Claudia
C
Barreira
Amilton A
AA
Marques
Wilson
W
D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D009185:Myelin Proteins / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation
D009185:Myelin Proteins; C073687:PMP22 protein, human
Braz J Med Biol Res. 2003 Oct;36(10):1403-7
14502374
Arch Neurol. 2006 Jan;63(1):112-7
16401743
Brain. 1997 Mar;120 ( Pt 3):465-78
9126058
Neuromolecular Med. 2006;8(1-2):43-62
16775366
Genet Med. 2001 Sep-Oct;3(5):335-42
11545686
Ann Neurol. 2006 Feb;59(2):358-64
16437560
Ann Neurol. 1998 May;43(5):680-3
9585367
Am J Med Genet A. 2008 Sep 15;146A(18):2412-6
18698610
J Neurol. 1999 Jul;246(7):596-9
10463363
J Neurol. 2005 Aug;252(8):972-9
15765265
Neurogenetics. 2005 Sep;6(3):159-63
15947997
J Neurol Neurosurg Psychiatry. 1997 Apr;62(4):310-8
9120441
Neurology. 1995 Nov;45(11):2090-3
7501164
Acta Neurol Scand. 2004 Sep;110(3):196-9
15285778
Ann Neurol. 2005 Apr;57(4):589-91
15786462