|
Title
|
|
|
|
Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a)
| |
|
Author
|
|
|
|
| |
|
Institution/Organisation
|
|
|
|
HMSN Collaborative Research Group
| |
|
Abstract
|
|
|
|
| Hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT 1) is an autosomal dominant disorder of the peripheral nervous system characterized by progressive weakness and atrophy of distal limb muscles. In the majority of HMSN I families, linkage studies localized the gene (CMT 1a) to the pericentromeric region of chromosome 17. We have detected with probe pVAW409R3 (D17S122) localized in 17p11.2 a duplication, co-segregating with the disease in 12 HMSN I families. In these families the duplication was present in all 128 patients but absent in the 84 unaffected and 44 married-in individuals (lod score of 58.44 at zero recombination). Further, on one HMSN I family the disease newly appeared simultaneously with a de novo duplication originating from an unequal crossing-over event at meiosis. Since different allelic combinations were found segregating with the duplication in different families linkage disequilibrium was not a significant factor. These findings led us to propose that the duplication in 17p11.2 itself is the disease causing mutation in all the HMSN I families analyzed. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Neuromuscular disorders
| |
|
Publication
|
|
|
|
1991
| |
|
ISSN
|
|
|
|
0960-8966
| |
|
Volume/pages
|
|
|
|
1
:2
(1991)
, p. 93-97
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (publisher's version - intranet only)
|
|
|
|
| |
|