The objective is to determine the disease severity in genetically proven CMT1A/HNPP patients and to correlate this with sequence variants in CMT and immunity related genes. Identification of genotype-phenotype correlations in CMT1A will allow…
ID
Source
Brief title
Condition
- Neurological disorders congenital
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The presence or absence of copy number variants (CNV) and sequence variants of
CMT genes and genes involved in the immune system between the most severely and
mildest affected patients.
Secondary outcome
not applicable
Background summary
Amongst hereditary neuropathies, Charcot-Marie-Tooth disease (CMT) or
hereditary motor and sensory neuropathy (HMSN), is the most prevalent. Over 30
loci and genes are identified. The most frequent demyelinating form (CMT1A) is
most often caused by a duplication of the PMP22 gene, whereas a deletion of one
copy of the PMP22 gene causes hereditary neuropathy with liability to pressure
palsies (HNPP). The variability of the CMT1A phenotype, even within families,
suggests the presence of modifiers but none have been identified thus far.
Study objective
The objective is to determine the disease severity in genetically proven
CMT1A/HNPP patients and to correlate this with sequence variants in CMT and
immunity related genes.
Identification of genotype-phenotype correlations in CMT1A will allow
prognostic counselling of the patients. Insight in modifiers of the disease
process may yield new therapeutic targets. Finally, this study will yield a
biobank of well-characterized neuropathy patients which is essential for future
studies on CMT.
Study design
Cross sectional study.
750 patients with known CMT1A duplication and 330 HNPP deletion patients will
be approached to complete a questionnaire Subsequently, the 100 most severely
and 100 mildest affected CMT1A patients and 50 HNPP patients at both ends of
the spectrum will be selected and invited to the hospital for detailed
neurological tests and DNA-analysis.
Study burden and risks
For most patients participation will only consist of completing a questionnaire
by telephone.
300 patients (200 CMT1A and 100 HNPP patients) who belong to the most severely
and the mildest affected patients, will be invited for a single hospital visit
with a duration of 2.5 hours. A family history will be taken. The following
tests will be applied: physical neurological examination, testing muscle
strength, testing sensibility, 4 tests of hand function, a 10 meter timed walk,
electrophysiological test of the ulnar nerve, a single blood draw and 3
questionnaires concerning daily activities and quality of life.
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
duplication or deletion of PMP22-gene,
age 12-60 year
Exclusion criteria
- Use of medication or suffering from other disease than CMT/HNPP that can cause neuropathy
- comorbidity interfering with mobility
- non-Caucasian patients
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL23232.018.08 |