RESUMEN
BACKGROUND AND PURPOSE: Autosomal Recessive Hereditary Spastic Paraplegia with Thin Corpus Callosum (AR-HSPTCC) is a clinically and genetically heterogeneous complicated form of spastic paraplegia. Two AR-HSPTCC loci have been assigned to chromosome 15q13-15 (SPG11) and chromosome 8p12-p11.21 respectively. Mutations in the SPG11 gene, encoding the spatacsin protein, have been found in the majority of SPG11 families. In this study, involvement of the SPG11 or 8p12-p11.21 loci was investigated in five Italian families, of which four consanguineous. METHODS: Families were tested for linkage to the SPG11 or 8p12-p11.21 loci and the SPG11 gene was screened in all the affected individuals. RESULTS: Linkage was excluded in the four consanguineous families. In the only SPG11-linked family the same homozygous haplotype 4.2 cM across the SPG11 locus was shared by all the three affected siblings. A novel c.2608A>G mutation predicted to affect the splicing was found in exon 14 of the SPG11 gene. DISCUSSION: This collection of families contributes to highlight the intra and inter locus heterogeneity in AR-HSPTCC, already remarked in previous reports. In particular, it confirms heterogeneity amongst Italian families and reports a new mutation predicted to affect splicing in the spatacsin gene.
Asunto(s)
Agenesia del Cuerpo Calloso/genética , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Malformaciones del Sistema Nervioso/genética , Proteínas/genética , Paraplejía Espástica Hereditaria/genética , Adolescente , Adulto , Agenesia del Cuerpo Calloso/metabolismo , Agenesia del Cuerpo Calloso/fisiopatología , Femenino , Humanos , Masculino , Malformaciones del Sistema Nervioso/metabolismo , Malformaciones del Sistema Nervioso/fisiopatología , Linaje , Proteínas/metabolismo , Paraplejía Espástica Hereditaria/metabolismo , Paraplejía Espástica Hereditaria/fisiopatología , Adulto JovenAsunto(s)
Adenosina Trifosfatasas/genética , Aberraciones Cromosómicas , Análisis Mutacional de ADN , Genes Dominantes/genética , Genética de Población , Paraplejía Espástica Hereditaria/genética , Adulto , Edad de Inicio , Anciano , Deleción Cromosómica , Codón sin Sentido/genética , Estudios Transversales , Femenino , Mutación del Sistema de Lectura/genética , Tamización de Portadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Mutagénesis Insercional/genética , Mutación Missense/genética , Fenotipo , Sitios de Empalme de ARN/genética , Paraplejía Espástica Hereditaria/epidemiología , EspastinaRESUMEN
BACKGROUND: EcoRI, MspI and RsaI restriction fragment length polymorphisms (RFLPs) of the COL1A2 (type I collagen) gene are proving to be extremely informative markers for describing human populations; therefore they hold considerable potential for anthropogenetic research. AIM: The objective of this study was to characterize at the DNA level the Colorado Indians from Ecuador, for whom only blood group frequency information is available, and to investigate their relationships with the Cayapa-another Ecuadoran Native American group belonging to the same linguistic affiliation-and other world populations. SUBJECTS AND METHODS: Colorado Indians (n = 80) were analysed for the three anthropologically informative RFLPs of the COL1A2 gene. To better define the genetic relationship between this group and other populations, principal component analysis (PCA) was performed and genetic distances were estimated. Population genetic structure was tested through analysis of molecular variance (AMOVA) by comparing haplotype frequencies. RESULTS: COL1A2 allele and haplotype frequencies showed a certain degree of heterogeneity between the two Chibchan populations of Ecuador. The AMOVA test detected a significant level of differentiation (Fst = 0.034, p = 0.0049) between Colorado and Cayapa Indians. PC and genetic distance analyses showed a clear-cut separation between African and non-African populations; within the latter, the two Native American groups were differentiated from each other. CONCLUSIONS: The present findings suggest the presence of a low level of genetic relatedness between the Colorado and the Cayapa, despite their supposed common ethnogenesis. This confirms what has been inferred from other genetic data about the high degree of heterogeneity among Native Americans, even within the same linguistic branch, thus supporting the existence of genetic sub-structure within the central and southern American populations.
