Methylation-specific multiplex ligation-dependant probe amplification (MS-MLPA) analysis showed hypermethylation of the SNRPN and NDN genes in the PWS/AS critical region of chromosome 15 in this patient.
Prader-Willi Syndrome (PWS) is a neurodevelopmental disease involving imprinted genes, including NDN, which are only expressed from the paternally inherited allele, with the maternally inherited allele silent.
Necdin is one of several genes inactivated in children with Prader-Willi syndrome, who are predisposed to increased adiposity at the expense of lean mass.
NDN is one of several genes inactivated in Prader-Willi syndrome (PWS), a developmental disorder characterized by obesity, hypotonia, and developmental delay.
Together, these results indicate that lack of necdin during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS.
It is caused by the absence of expression of the active paternal genes such as the SNRPN, NDN, and possibly others in the PWS critical region on 15q11-13.
This imprinted region is implicated in the pathogenesis of Prader-Willi syndrome (PWS), a neurodevelopmental disorder, where NDN is one of multiple genes silenced by deletion, maternal uniparental disomy or translocation.
We report first that Necdin-deficiency in mice induces central respiratory deficits reminiscent of Prader-Willi syndrome (irregular rhythm, frequent apneas, and blunted respiratory regulations), second that Necdin is expressed by medullary serotonergic neurons, and third that Necdin deficiency alters the serotonergic metabolism, the morphology of serotonin vesicles in medullary serotonergic neurons but not the number of these cells.
We further suggest that loss of necdin contributes to the neurological phenotype of PWS, and raise the possibility that co-deletion of necdin and the related protein Magel2 may explain the lack of single gene mutations in PWS.
However, we demonstrate that the IC, if required for imprinted regulation, is not involved in the spatio-temporal regulation of distantly located retrotransposed genes such as the Ndn gene in the PWS domain.
The human necdin gene in chromosome 15q11-q12 is maternally imprinted, paternally transcribed, and not expressed in Prader-Willi syndrome, a human genomic imprinting-associated neurodevelopmental disorder.
Four protein-encoding genes (MKRN3, MAGEL2, NDN and SNURF-SNRPN) and several small nucleolar (sno) RNA genes (HBII-13, HBII-436, HBII-85, HBII-438A, HBII-438B and HBII-52) are expressed from the paternal chromosome only but their contribution to PWS is unclear.
We propose that necdin deficiency may contribute to observed respiratory abnormalities in individuals with Prader-Willi syndrome through a similar suppression of central respiratory drive.