Title
A de novo duplication in 17p11.2 and a novel mutation in the <tex>$P_{o}$</tex> gene in two Déjérine-Sottas syndrome patients
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
New York, N.Y. ,
Subject
Human medicine
Source (journal)
Human mutation. - New York, N.Y.
Volume/pages
8(1996) :4 , p. 304-310
ISSN
1059-7794
ISI
A1996VV88000002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Dejerine-Sottas syndrome (DSS), or hereditary motor and sensory neuropathy (HMSN) type III, is a severe hypertrophic demyelinating neuropathy with infantile onset. The clinical symptoms are similar to those found in Charcot-Marie-Tooth disease type 1 (CMT1) or HMSN type I patients, but they are more severe. DSS is genetically heterogeneous, Dominant mutations in two major peripheral myelin protein genes, PMP22 and P-0, are associated with a DSS phenotype. Mutations in the same genes are also responsible for the CMT1 phenotype. A 1.5 Mb duplication in 17p11.2 is the major mutation found in familial and sporadic CMT1 patients. We studied two genetically sporadic DSS patients. The presence of a de novo duplication in one patient was revealed by Southern blot analysis, using polymorphic markers located in the duplicated area. The 17p11.2 allele segregation in this patient and in her parents suggests that the duplication is of maternal origin, In the other patient, single strand conformation polymorphism (SSCP) analysis of the 6 exons of the P-0 gene revealed two additional bands in exon 3. Sequencing of this exon identified a novel dominant mutation replacing a sequence of 8 bp by a mutated sequence of 5 bp, The mutation apparently leads to the replacement of 4 amino acids at positions 86-89 by three different amino acids, in an area that is part of a predicted beta-strand. Our findings support the suggestion that DSS and CMT1 disease should not be considered as two different clinical entities. (C) 1996 Wiley-Liss, Inc.
E-info
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