H244r

unidentified

Italian

*Mutations identified subsequent to Zeng et al, 2002; Novel mutations are underlined.

*Mutations identified subsequent to Zeng et al, 2002; Novel mutations are underlined.

3.3. Genotype: Phenotype Correlations

While all patients presented with severe psychomotor delay, poor head control and truncal hypotonia and developed progressive spasticity and macrocephaly, the clinical onset and time appearance of seizures varied. Clinical manifestations were noted at birth in two youngsters of British ancestry, both of who possessed one allele containing the D249V substitution. Both died early. Another infant with an onset at birth carried the E214X mutation which produces a stop codon.

Several other novel mutations were associated with an onset before two or three months and early seizures. These include V14G, C152W, P181L, 244 del AT, X314W, 698 inc C and 923 del T. In several of these examples, either a stop codon is introduced or eliminated or a frameshift occurs. In the case of the C152W mutation, a disulphide bond critical for the molecular conformation of ASPA is disrupted. Therefore, clinical variations in Canavan disease may result from differing effects exerted on the expression of ASPA activity by specific mutations.

Table 4. Results of Mutation Analysis in 39 Non-Jewish CD Patients*

Summary

n

Mutations

Missense mutations

0 0

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