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

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• 作者：Raquel Rodr&#237 ; guez-Ló ; pez^a ; ^{raquel.rodriguezl@ses.juntaextremadura.net} ; José ; M. Carbonell Pé ; rez^a ; Ará ; nzazu Margallo Balsera^a ; Guillermo Gervasini Rodr&#237 ; guez^b ; Trinidad Herrera Moreno^a ; Mayte Garc&#237 ; a de Cá ; ceres^a ; Marta Gonzá ; lez-Carpio Serrano^a ; Felipe Casanueva Freijo^c ; Juan Ramó ; n Gonzá ; lez Ruiz^d ; Francisco Barros Angueira^e ; Pilar Mé ; ndez Pé ; rez^f ; Manuela Nú ; ñ ; ez Esté ; vez^f ; Enrique Galá ; n Gó ; mez^f
• 关键词：BDNF ; brain-derived neurotrophic factor gene ; Bdnf ; brain-derived neurotrophic factor protein ; BMI ; body mass index ; CAT ; chloramphenicol acetyltransferase gene ; CD44 ; CD44 antigen gene ; CD59 ; CD59 antigen gene ; ChAS ; The Affymetrix® ; Chromosome Analys
• 刊名：Gene
• 出版年：2013
• 出版时间：10 March, 2013
• 年：2013
• 卷：516
• 期：2
• 页码：285-290
• 全文大小：471 K

文摘

Individuals who are carriers of deletions of various sizes that cause haploinsufficiency in the contiguous m>WT1m> and m>PAX6m> genes, located on chromosome 11p13 approximately 4 Mb centromeric to the m>BDNFm> 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 m>dnm> 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 m>BDNFm>. The relationship between genetic variation based on the genotype combinations of the 4 gene SNPs tagging the m>BDNFm> 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 m>BDNFm> 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 (m>BDNFm>) 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 m>BDNFm> gene could constitute an adequate model to study in depth their effects.