Communicated by Martin Bobrow
below knee amputations for severe foot deformities. All affected individuals had distal muscle weakness and wasting of upper and lower limbs, tendon stretch hypo/areflexia, and distal sensory impairment. The mean median nerve motor conduction velocity of affected family members was 11.1 m/s and median sensory nerve action potentials (SNAPs) were consistently absent. The clinical impression was therefore that the disorder in this family was significantly more severe than in other HMSN type I families in the study.
Blood samples were available from 15 members of this family. Eight of them are affected.
Methods
Restriction fragment length polymorphisms (RFLPs) were recognised by chromosome 17p11.2 DNA markers: VAW409R3A (D17S122) and p132G8RI (PMP22). Southern blot analysis was performed according to standard procedure. Primers flanking the CA repeat polymorphisms RM11-GT (D17S122), Mfd3 (APOA2), and Mfd67 (D1S104), and the conditions of the polymerase chain reaction were as previously described (Buetow et al., 1990;Weber et al., 1990). Lod scores were computed with the ILINK component of LINKAGE program (Lathrop et al., 1984).
The coding region of the P0 gene was amplified using previously reported six primer sets (Nelis et al., 1994b). The standard polymerase chain reaction (PCR) was carried out in the presence of Γ33P-dATP (Amersham). Samples were subjected to electrophoresis on a 1X Hydrolink MDE gel at 15 W for 20 hr. Genomic DNA from 50 unrelated control subjects were included in this analysis.
The PCR product was purified using the Gene-