ABSTRACT
This paper presents some of the results of our studies on two distinct groups of disorders: Muscular dystrophies and craniofacial conditions. Among the first, we focused on autosomal recessive (AR) limb-girdle muscular dystrophies (LGMD). To date, there are 8 known loci associated with AR LGMD (LGMD2A, LGMD2B to 2H). We were able to map 2 of these 8 genes through the analysis of large Brazilian families. We also classified 140 patients into one of the seven AR LGMD forms: LGMD2B is the mildest and a clear phenotype-genotype correlation was not observed in most of the cases. Molecular studies on craniofacial disorders have been recently initiated, as exemplified in the text with a discussion on craniosynostosis and cleft lip and/or palate (CL/P). The study of Brazilian patients with craniosynostosis caused by mutations in fibrobrast growth receptor genes (FGFR1-3) allowed us to identify some Apert and Pfeiffer patients with unusual mutations. In addition, about 10 percent of Brazilian patients with coronal synostosis seem to be due to a specific mutation within FGFR3. Finally, our molecular studies on CL/P patients excluded two genes (one, a transforming growth factor and the other involved in folate metabolism) as major candidates for this common malformation. Further studies are being conducted in all the disorder presented in this paper.
Subject(s)
Humans , Male , Female , Craniofacial Abnormalities/genetics , Genes, Recessive , Muscular Dystrophies/genetics , Brazil , Cleft Palate/genetics , Craniofacial Dysostosis/genetics , PhenotypeABSTRACT
Uma família com três afetados por distrofia tipo Duchenne (DMD) na qual a mäe e uma de suas filhas tinham sinais clínicos de DMD, foi seguida durante 14 anos. A mäe afetada tinha um quadro clínico semelhante a distrofia muscular tipo Becker ou tipo cinturas. Aos 50 anos de idade ela näo conseguia subir escadas e ela parou de andar aos 52 anos. Uma de suas filhas, com idade atual de 32 anos, tem hipertrofia das panturrilhas e altos níveis de creatino-cinase (CK) e piruvato-cinase (PK) desde os 16 anos de idade. Várias hipóteses säo discutidas para explicar a ocorrência de sinais clínicos em duas ou mais portadoras pertencentes à mesma genealogia