title: Mapping of the familial infantile myasthenia (congenital myasthenic syndrome type Ia) gene to chromosome 17p with evidence of genetic homogeneity.
abstract: Familial infantile myasthenia is an autosomal recessive disorder, recently classified as congenital myasthenic syndrome type Ia. Onset of symptoms is at birth to early childhood with significant myasthenic weakness and possible respiratory distress, followed later in life by symptoms of mild to moderate myasthenia. Thirty-six patients of 12 families, seven of them consanguineous, were used to map the familial infantile 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 chromosome 17p. A maximum lod score of 9.28 at theta = 0.034 was obtained between the disease locus and marker locus D17S1537. Haplotype analysis showed all families to be consistent with linkage to this region thus providing evidence for genetic homogeneity of familial infantile myasthenia. Multipoint linkage analysis mapped the disease gene in the approximately 4.0 cM interval between marker loci D17S1537 and D17S1298 with a maximum multipoint lod score of 12.07. Haplotype analysis and homozygosity by descent in affected individuals of the consanguineous families revealed results in agreement with the confinement of the familial infantile myasthenia region within the interval between marker loci D17S1537 and D17S1298.
authors.affiliation: The Cyprus Institute of Neurology and Genetics, Nicosia.
authors.forename: K
authors.initials: K
authors.lastname: Christodoulou
authors.forename: M
authors.initials: M
authors.lastname: Tsingis
authors.forename: F
authors.initials: F
authors.lastname: Deymeer
authors.forename: P
authors.initials: P
authors.lastname: Serdaroglu
authors.forename: C
authors.initials: C
authors.lastname: Ozdemir
authors.forename: A
authors.initials: A
authors.lastname: Al-Shehab
authors.forename: C
authors.initials: C
authors.lastname: Bairactaris
authors.forename: I
authors.initials: I
authors.lastname: Mavromatis
authors.forename: I
authors.initials: I
authors.lastname: Mylonas
authors.forename: A
authors.initials: A
authors.lastname: Evoli
authors.forename: K
authors.initials: K
authors.lastname: Kyriallis
authors.forename: L T
authors.initials: LT
authors.lastname: Middleton
mesh_terms: D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D019083:Mediterranean Region; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018895:Microsatellite Repeats / Q000235:genetics; D009157:Myasthenia Gravis / Q000151:congenital* / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D050683:R-SNARE Proteins; D016615:Telomere / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins