Distinct mechanism of formation of the 48, XXYY karyotype.

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.

The modifier effect of the BDNF gene in the phenotype of the WAGRO syndrome.

Individuals who are carriers of deletions of various sizes that cause haploinsufficiency in the contiguous WT1 and PAX6 genes, located on chromosome 11p13 approximately 4 Mb centromeric to the BDNF gene, are susceptible to Wilms tumor, aniridia, mental retardation, genitourinary anomalies and obesity (WAGRO syndrome). The molecular characterization of the wide deletion 11p15.1p12 arr (18676926-36576388) x1 dn in a child with 3 years and 4 months of age only affected by aniridia, predicts not only other serious associated diseases, but also allows us to hypothesize a specific phenotype of mental impairment, conduct alterations and childhood obesity, possibly added to the onset of metabolic alterations. The variable appearance and/or description of haploinsufficiency for obesity susceptibility in the WAGR syndrome mainly depends on the critical region located within 80 kb of exon 1 of BDNF. The relationship between genetic variation based on the genotype combinations of the 4 gene SNPs tagging the BDNF gene and the body mass index (BMI) was studied. The polymorphic variability was similarly distributed in 218 children suffering a severe and non-syndromic obesity from families at high risk for obesity, as compared with 198 controls. The corroborated role of the BDNF gene as highly susceptible to severe syndromic obesity has not already been evidenced in the molecular basis of overweight attributed to the common polygenic principles. Its potential role as risk modifier variant to provoke more severe phenotype has not yet been demonstrated. Some genetic variants of brain-derived neurotrophic factor (BDNF) have resulted in important disorders of energy balance, but it is essential to know exactly their deleterious human capacity because they play a fundamental role in the development and plasticity of the central nervous system in regulating food intake. The existence of polymorphic amino acid changes of unknown functional significance in patients carrying the haploinsufficiency of the BDNF gene could constitute an adequate model to study in depth their effects.