Spastic paraplegia, optic atrophy, and neuropathy: new observations, locus refinement, and exclusion of candidate genes.
SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with marker D11S1889). Three genes located in this newly defined critical region were sequenced, but no pathogenic mutation was detected. The gene responsible for SPOAN remains elusive.
Macedo-Souza
Lúcia Inês
LI
Human Genome Research Center, Institute of Biosciences, University of São Paulo (USP), São Paulo, Brazil.
Kok
Fernando
F
Santos
Silvana
S
Licinio
Luciana
L
Lezirovitz
Karina
K
Cavaçana
Natale
N
Bueno
Clarissa
C
Amorim
Simone
S
Pessoa
André
A
Graciani
Zodja
Z
Ferreira
Aurea
A
Prazeres
Abdísio
A
de Melo
Aurea Nogueira
AN
Otto
Paulo Alberto
PA
Zatz
Mayana
M