RESUMEN
The MSH2 c.388_389del mutation has occasionally been described in Lynch families worldwide. At the Portuguese Oncology Institute in Porto, Portugal, we have identified 16 seemingly unrelated families with this germline mutation. To evaluate if this alteration is a founder or a recurrent mutation we performed haplotype analysis in the 16 Portuguese index cases and 55 relatives, as well as in four index cases and 13 relatives reported from Germany, Scotland, England, and Argentina. In the Portuguese families we observed a shared haplotype of approximately 10 Mb and all were originated from the north of Portugal. These results suggest that this alteration is a founder mutation in Portugal with a relatively recent origin. In the reported families outside Portugal with this mutation different haplotype backgrounds were observed, supporting the hypothesis that it occurred de novo on multiple occasions. We also conclude that the high proportion of families with the MSH2 c.388_389del mutation indicates that screening for this alteration as a first step may be cost-effective in the genetic testing of Lynch syndrome suspects of Portuguese ancestry, especially those originating from the north of Portugal.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Efecto Fundador , Proteína 2 Homóloga a MutS/genética , Eliminación de Secuencia , Argentina , Secuencia de Bases , Inglaterra , Mutación de Línea Germinal , Alemania , Haplotipos , Humanos , Repeticiones de Microsatélite , Motivos de Nucleótidos , Polimorfismo de Nucleótido Simple , PortugalRESUMEN
Lipid studies were performed on fasting plasma samples in 214 healthy adolescent boys, 11-19 years of age. Ranges of normal values for plasma cholesterol and triglyceride concentrations, and normal lipoprotein patterns were established for this age group. The boys were grouped according to puberty rating. A significant increase in triglyceride values was obtained with adolescent maturity. Plasma cholesterol values did not change with age or puberty rating. One boy had hypercholesterolemia and a lipoprotein pattern consistent with Type II hyperlipoproteinemia (Fredrickson). Seventeen boys, all of whom had reached adolescent maturity, had elevated triglyceride values and a marked increase in pre-beta-lipoprotein. It appears from this study that increased concentrations of triglyceride and Type IV hyperlipoproteinemia of Fredrickson may be detected as boys reach maturity at adolescence.