Small mosaic deletion encompassing the snoRNAs and SNURF‐SNRPN results in an atypical Prader–Willi syndrome phenotype. Issue 2 (5th December 2013)

• Record Type: Journal Article
• Authors: Anderlid, Britt‐Marie; Lundin, Johanna; Malmgren, Helena; Lehtihet, Mikael; Nordgren, Ann
• Is Part Of: American journal of medical genetics. Volume 164:Issue 2(2014.)
• Page Start: 425
• Page End: 431
• Publication Date: 2013-12-05
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36307
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="ajmga36307-sec-0001" sec-type="section"> <p>Genetic analyses were performed in a male patient with suspected Prader–Willi syndrome who presented with hypogonadism, excessive eating, central obesity, small hands and feet and cognition within the low normal range. However, he had no neonatal hypotonia or feeding problems during infancy. Chromosome analysis showed a normal male karyotype. Further analysis with array‐CGH identified a mosaic 847 kb deletion in 15q11‐q13, including <italic>SNURF‐SNRPN</italic>, the snoRNA gene clusters SNORD116 (HBII‐85), SNORD115, (HBII‐52), SNORD109 A and B (HBII‐438A and B), SNORD64 (HBII‐13), and <italic>NPAP1</italic> (<italic>C15ORF2</italic>). MLPA confirmed the deletion and the results were compatible with a paternal origin. Metaphase‐FISH verified the mosaicism with the deletion present in 58% of leukocytes analyzed. Three smaller deletions in this region have previously been reported in patients with Prader–Willi syndrome phenotype. All three deletions included SNORD116, but only two encompassed parts of <italic>SNURF‐SNRPN</italic>, implicating SNORD116 as the major contributor to the Prader–Willi phenotype. Our case adds further information about genotype–phenotype correlation and supports the hypothesis that SNORD116 plays a major role in the pathogenesis of Prader‐Willi syndrome. Furthermore, it examplifies diagnostic difficulties in atypical cases and illustrates the need for additional testing methods when Prader‐Willi syndrome is suspected. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>