RESUMO
Hereditary spastic paraplegias (HSPs) form a heterogeneous group of neurological disorders. A whole-genome linkage mapping effort was made with three HSP-affected families from Spain, Portugal, and Tunisia and it allowed us to reduce the SPG26 locus interval from 34 to 9 Mb. Subsequently, a targeted capture was made to sequence the entire exome of affected individuals from these three families, as well as from two additional autosomal-recessive HSP-affected families of German and Brazilian origins. Five homozygous truncating (n = 3) and missense (n = 2) mutations were identified in B4GALNT1. After this finding, we analyzed the entire coding region of this gene in 65 additional cases, and three mutations were identified in two subjects. All mutated cases presented an early-onset spastic paraplegia, with frequent intellectual disability, cerebellar ataxia, and peripheral neuropathy as well as cortical atrophy and white matter hyperintensities on brain imaging. B4GALNT1 encodes ß-1,4-N-acetyl-galactosaminyl transferase 1 (B4GALNT1), involved in ganglioside biosynthesis. These findings confirm the increasing interest of lipid metabolism in HSPs. Interestingly, although the catabolism of gangliosides is implicated in a variety of neurological diseases, SPG26 is only the second human disease involving defects of their biosynthesis.
Assuntos
Disfunção Cognitiva/genética , Gangliosídeos/biossíntese , Paraplegia Espástica Hereditária/genética , Adolescente , Adulto , Idade de Início , Brasil , Ataxia Cerebelar/genética , Criança , Pré-Escolar , Mapeamento Cromossômico/métodos , Exoma , Feminino , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Gangliosídeos/genética , Predisposição Genética para Doença , Alemanha , Homozigoto , Humanos , Lactente , Metabolismo dos Lipídeos , Masculino , Mutação de Sentido Incorreto , Linhagem , Portugal , Espanha , Paraplegia Espástica Hereditária/metabolismo , Tunísia , Adulto JovemRESUMO
BACKGROUND: Hevea brasiliensis, a member of the Euphorbiaceae family, is the major commercial source of natural rubber (NR). NR is a latex polymer with high elasticity, flexibility, and resilience that has played a critical role in the world economy since 1876. RESULTS: Here, we report the draft genome sequence of H. brasiliensis. The assembly spans ~1.1 Gb of the estimated 2.15 Gb haploid genome. Overall, ~78% of the genome was identified as repetitive DNA. Gene prediction shows 68,955 gene models, of which 12.7% are unique to Hevea. Most of the key genes associated with rubber biosynthesis, rubberwood formation, disease resistance, and allergenicity have been identified. CONCLUSIONS: The knowledge gained from this genome sequence will aid in the future development of high-yielding clones to keep up with the ever increasing need for natural rubber.