title: Spastic paraplegia, optic atrophy, and neuropathy is linked to chromosome 11q13.
abstract: We report an autosomal recessive neurodegenerative disorder in 25 white members from a large inbred Brazilian family, 22 of whom were evaluated clinically. This condition is characterized by (1) subnormal vision secondary to apparently nonprogressive congenital optic atrophy; (2) onset of progressive spastic paraplegia in infancy; (3) onset of progressive motor and sensory axonal neuropathy in late childhood/early adolescence; (4) dysarthria starting in the third decade of life; (5) exacerbated acoustic startle response; and (6) progressive joint contractures and spine deformities. Motor handicap was severe, and all patients were wheelchair bound after 15 years old. We performed a genome-wide screen including 25 affected individuals and 49 of their unaffected relatives. Linkage was detected at 11q13 region with a maximum logarithm of odds score of +14.43, obtained with marker D11S1883. The candidate region, which lies between D11S1908 and D11S1889, encompasses approximately 4.8Mb and has more than 100 genes and expressed sequences. We propose the acronym SPOAN (spastic paraplegia, optic atrophy, and neuropathy) for this complex syndrome.
authors.affiliation: Department of Biology, Institute of Biological Sciences and Center for Study of Human Genome, University of São Paulo, Brazil.
authors.forename: Lucia I
authors.initials: LI
authors.lastname: Macedo-Souza
authors.forename: Fernando
authors.initials: F
authors.lastname: Kok
authors.forename: Silvana
authors.initials: S
authors.lastname: Santos
authors.forename: Simone C
authors.initials: SC
authors.lastname: Amorim
authors.forename: Alessandra
authors.initials: A
authors.lastname: Starling
authors.forename: Agnes
authors.initials: A
authors.lastname: Nishimura
authors.forename: Karina
authors.initials: K
authors.lastname: Lezirovitz
authors.forename: Angelina M M
authors.initials: AM
authors.lastname: Lino
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001938:Brazil; D002648:Child; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D018450:Disease Progression; D004401:Dysarthria / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006801:Humans; D007596:Joints / Q000002:abnormalities; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D015418:Optic Atrophies, Hereditary / Q000235:genetics*; D010264:Paraplegia / Q000235:genetics*; D010375:Pedigree; D013216:Reflex, Startle / Q000502:physiology; D013131:Spine / Q000002:abnormalities
chemical_list: D004247:DNA