The above mentioned symptoms, especially with an X-chromosomal pattern of inheritance.
Hereditary Motor and Sensory Neuropathy, HMSNX, CMTX1, CMTX5 - Cx32, GJB1, PRPS1
Clinical Features
The clinical features of the X-chromosomal inherited form of hereditary motor-sensory neuropathy (HMSNX, CMTX1) are, in men, almost identical to those of the autosomal dominant form of HMSN. Affected women often exhibit mild or no clinical symptoms.
Patients exhibit a progressive, predominantly motor, demyelinating and/or axonal neuropathy with a measurable delay in nerve conduction velocity (23 - 40 ms). Symmetrical atrophic paresis begins in the musculature of the foot and lower leg. Muscle reflexes often expire before the onset of paralysis. Distal sensory impairment is usually less pronounced than motor symptoms. Painful dysaesthesia and vasomotor impairment also occur. Many patients exhibit clinical symptoms in childhood; almost all manifest the disease before age 30. In rare cases, a later age of onset has also been observed.
Genetic Information
This, the most common X-chromosomal inherited form of HMSN (CMTX), is caused by mutation in the Connexin 32 gene (Cx32, Gap Junction Protein Beta 1, GJB1) located on chromosome Xq13.1 and affects mostly men. Transmission from father to son is excluded.
Sequence analysis reveals that 90% of CMTX patients have a mutation in the Cx32 gene. A deletion of the entire gene has also been described.
Prevalence
Approx. 1 : 100 000
Diagnostic
Indication
Method
All exons as well as their flanking regions in the Cx32 gene are analysed using DNA sequencing.
Deletions and/or duplications of one or more exons are captured using MLPA.
Sample Requirement
2 - 4 ml of EDTA blood
Duration
4 - 6 weeks