The smallest paternally transmitted Snord 116 deletion in a young female displays a typical PWS phenotype

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 697-707-Obesity Pathophysiology
Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-705
Sanaa Eddiry Jr.*1, Eric Bieth2, Françoise Lorenzini2, Veronique Gaston2, Alexandre Buffet2, Françoise Conte Auriol2, Catherine Molinas2, Benoit Arveiler3, Jean-Pierre Salles4 and Maite Tauber5
1INSERM, Toulouse, France, 2CHU Toulouse, 3CHU Bordeaux, 4CHU/Hopital Des Enfants, Toulouse Cedex, France, 5Hopital des Enfants, Toulouse Cedex, France
Background: Prader-Willi syndrome (PWS) is a rare disorder arising from the lack of expression of paternal alleles in the chromosomal region 15q11-13. Three clinical cases with microdeletion without abnormal DNA methylation profile at the SNURF-SNRPN locus have been recently reported supporting the role of the snord 116 gene locus in the pathophysiology of this complex disease.

Clinical case: We report the case of a 23-years old woman, of Caucasian origin, born from non-consanguineous parents.

The patient was born after 36 weeks of gestation, by a scheduled C-section because of the presence of last trimester polyhydramnios. Birth weight was 2780 g, length 48 cm and head circumference 35 cm. Severe neonatal hypotonia was noted after birth with poor suckling requiring complete nasogastric tube feeding for the first 2 weeks of life when she stayed one month in the hospital. Brain CT scan and karyotype were normal at birth from a first wedding, the father had had a healthy daughter who had 2 healthy children and refused to undergo a genetic analysis. The father’s brother and his parents who were asymptomatic, were dead. A first baby born from the couple was a preterm girl who died for unknown reasons on the fourth day of life and presented a severe hypotonia.

The patient was admitted in our reference centre for PWS when she was 23. Height was 155 cm (-1.5 SD, 6.5 cm below her target height), weight 75 kg, BMI 31.2 kg/m2 and head circumference 59 cm (+2.5 SD). She was blond haired with narrow front and had mild dysmorphic features. She has no autonomy to control her hyperphagia and displays temper tantrums with difficulties for planification. Her endocrine evaluation confirmed a growth hormone deficiency, hypotonia and hypothyroidism.

We therefore underwent a diagnostic testing for PWS starting with a methyl specific PCR based at the SNURF-SNRPN locus which was normal. Because we considered she presented a PWS consistent phenotype we decided to complete the genetic study by performing a 15q11q12 QMPSF assay (Quantitative Multiplex PCR of Short fluorescent Fragment) that we developed to search for the presence of atypic deletions in PWS patients, which showed a 118 kbp microdeletion in the Snord116 locus associated to a normal DNA methylation prolife at the SNURF-SNRPN locus in blood cells.

Conclusion: We confirmed that the small region for PWS including the snord 116 gene drives the PWS phenotype in human and that deletion of the snord116 gene locus should be searched in all patients with PW-like syndrome.

Nothing to Disclose: SE Jr., EB, FL, VG, AB, FC, CM, BA, JPS, MT

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm