Expression and imprinting of MAGEL2 suggest a role in Prader-willi syndrome and the homologous murine imprinting phenotype.
Prader-Willi syndrome ( PWS ) is caused by the loss of expression of imprinted genes in chromosome 15q11-q13 . Affected individuals exhibit neonatal hypotonia , developmental delay and childhood-onset obesity . Necdin , a protein implicated in the terminal differentiation of neurons , is the only PWS candidate gene to reduce viability when disrupted in a mouse model . In this study , we have characterized MAGEL2 ( also known as NDNL1 ) , a gene with 51 % amino acid sequence similarity to necdin and located 41 kb distal to NDN in the PWS deletion region . MAGEL2 is expressed predominantly in brain , the primary tissue affected in PWS and in several fetal tissues as shown by northern blot analysis . MAGEL2 is imprinted with monoallelic expression in control brain , and paternal-only expression in the central nervous system as demonstrated by its lack of expression in brain from a PWS-affected individual . The orthologous mouse gene ( Magel2 ) is located within 150 kb of NDN  , is imprinted with paternal-only expression and is expressed predominantly in late developmental stages and adult brain as shown by northern blotting , RT-PCR and whole-mount RNA in situ hybridization . Magel2 distribution partially overlaps that of NDN  , with strong expression being detected in the central nervous system in mid-gestation mouse embryos by in situ hybridization . We hypothesize that , although loss of necdin expression may be important in the neonatal presentation of PWS , loss of MAGEL2 may be critical to abnormalities in brain development and dysmorphic features in individuals with PWS . .
