title: The modifier effect of the BDNF gene in the phenotype of the WAGRO syndrome.
abstract: 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.
authors.affiliation: Genetics Unit, Infanta Cristina Hospital, Badajoz, Spain. raquel.rodriguezl@ses.juntaextremadura.net
authors.forename: Raquel
authors.initials: R
authors.lastname: Rodríguez-López
authors.forename: José M Carbonell
authors.initials: JM
authors.lastname: Pérez
authors.forename: Aránzazu Margallo
authors.initials: AM
authors.lastname: Balsera
authors.forename: Guillermo Gervasini
authors.initials: GG
authors.lastname: Rodríguez
authors.forename: Trinidad Herrera
authors.initials: TH
authors.lastname: Moreno
authors.forename: Mayte
authors.initials: M
authors.lastname: García de Cáceres
authors.forename: Marta González-Carpio
authors.initials: MG
authors.lastname: Serrano
authors.forename: Felipe Casanueva
authors.initials: FC
authors.lastname: Freijo
authors.forename: Juan Ramón González
authors.initials: JR
authors.lastname: Ruiz
authors.forename: Francisco Barros
authors.initials: FB
authors.lastname: Angueira
authors.forename: Pilar Méndez
authors.initials: PM
authors.lastname: Pérez
authors.forename: Manuela Núñez
authors.initials: MN
authors.lastname: Estévez
authors.forename: Enrique Galán
authors.initials: EG
authors.lastname: Gómez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000502:physiology; D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D060045:Genes, Modifier / Q000502:physiology; D006801:Humans; D059785:Karyotype; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D017624:WAGR Syndrome / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor