Balsera A.M.,Genetics Unit |
Estevez M.N.,Unit of Genetic Pediatrics |
Beltran E.B.,Genetics Unit |
Sanchez-Giralt P.,Endocrinologist Service |
And 6 more authors.
Molecular Cytogenetics | Year: 2013
Background: To expose the unusual nature of a coincident sex chromosomal aneuploidy in a patient and his father. Molecular mechanisms involved probably are based on the sperm chromosome of paternal origin, which determine the mode of formation. Conventional cytogenetics techniques and multiple Quantitative Fluorescent PCR of STR markers in sexual chromosomes in the patient and his parents. Results: 48,XXYY and 47,XYY aneuploidies in the patient and his father, respectively, were identified. The additional X and Y chromosomes showed parental origin. Conclusions: An infrequent origin of the 48,XXYY syndrome was demonstrated. Mostly, it is thought to result from an aneuploid sperm produced through two consecutive non disjunction events in both meiosis I and II in a chromosomally normal father, but in our father's patient a 47,XYY was discovered. It is suggested that a higher incidence of 24,XY and 24,YY sperm may be possible in 47,XYY individuals andan increased risk for aneuploidy pregnancies may exist. Although 48,XXYY patients and Klinefelter syndrome are often compared, recently they are regarded as a distinct genetic and clinical entity. © 2013 Balsera et al.; licensee BioMed Central Ltd. Source
Albuquerque D.,University of Coimbra |
Estevez M.N.,Unit of Genetic Paediatrics |
Vibora P.B.,Endocrinologist Service |
Giralt P.S.,Endocrinologist Service |
And 11 more authors.
Annals of Human Genetics | Year: 2014
We screened for mutations in the MC4R and LEPR genes and investigated the genotype-phenotype correlation in obese individuals belonging to families with evident hereditary patterns of severe and early-onset obesity among the Iberian population. A total of 202 unrelated and severely obese patients since childhood, were enrolled in the study. Bidirectional sequencing of the MC4R gene was carried out in all patients; the LEPR gene was sequenced in 15 individuals based on additional clinical signals. Segregation analysis and/or genotype-phenotype description was performed for subjects with the new mutations and with presumably functional variants. Ten MC4R gene mutations were identified in the heterozygous state in 10 patients. Mutations p.R147G and p.G323E are new and mutations p.R7H, p.G32E, p.H76R, p.V103I, p.S127L, p.T150I, p.I251L and p.G252S were previously described. A new dinucleotide insertion -77_-76insTA in the promoter region of the LEPR gene was found in the heterozygous state in one patient. The new p.R147G and the previously published p.R7H, p.S127L, p.T150I and p.G252S MC4R mutations, cosegregate with obesity in our patients and were predicted to be deleterious. For the novel MC4R p.G323E and LEPR -77_-76insTA gene mutations, the genotype-phenotype correlation and bioinformatic analysis did not clarify whether these mutations are indeed implicated in obesity. © 2014 John Wiley & Sons Ltd/University College London. Source