MAPPING OF THE FAMILIAL INFANTILE MYASTHENIA (CONGENITAL MYASTHENIC SYNDROME TYPE IA) GENE TO CHROMOSOME 17P WITH EVIDENCE OF GENETIC HOMOGENEITY

Familial infantile myasthenia is an autosomal recessive disorder, rece ntly classified as congenital myasthenic syndrome type la, Onset of sy mptoms is at birth to early childhood with significant myasthenic weak ness and possible respiratory distress, followed later in life by symp toms of mild to moderate myasthenia, Thirty-six patients of 12 familie s, seven of them consanguineous, were used to map the familial infanti le myasthenia gene. A combination of linkage search through the genome , DNA pooling and homozygosity mapping were employed resulting in the localisation of this disease locus to the telomeric region of chromoso me 17p. A maximum led score of 9.28 at theta = 0.034 was obtained betw een the disease locus and marker locus D17S1537, Haplotype analysis sh owed all families to be consistent with linkage to this region thus pr oviding evidence for genetic homogeneity of familial infantile myasthe nia. Multipoint linkage analysis mapped the disease gene in the simila r to 4.0 cM interval between marker loci D17S1537 and D17S1298 with a maximum multipoint lod score of 12.07. Haplotype analysis and homozygo sity by descent in affected individuals of the consanguineous families revealed results in agreement with the confinement of the familial in fantile myasthenia region within the interval between marker loci D17S 1537 and D17S1298.