TY - JOUR
T1 - A novel deletion of SNURF/SNRPN exon 1 in a patient with Prader-Willi-like phenotype
AU - Cao, Yang
AU - AlHumaidi, Susan S.
AU - Faqeih, Eissa A.
AU - Pitel, Beth A.
AU - Lundquist, Patrick
AU - Aypar, Umut
N1 - Publisher Copyright:
© 2017 Elsevier Masson SAS
PY - 2017/8
Y1 - 2017/8
N2 - Here we report the smallest deletion involving SNURF/SNRPN that causes major symptoms of Prader-Willi syndrome (PWS), including hypotonia, dysmorphic features, intellectual disability, and obesity. A female patient with the aforementioned and additional features was referred to the Mayo Clinic Cytogenetics laboratory for genetic testing. Chromosomal microarray analysis and subsequent Sanger sequencing identified a de novo 6.4 kb deletion at 15q11.2, containing exon 1 of the SNURF gene and exon 1 of the shortest isoform of the SNRPN gene. SNURF/SNRPN exon 1, which is methylated on the silent maternal allele, is associated with acetylated histones on the expressed paternal allele. This region also overlaps with the PWS-imprinting center (IC). Subsequent molecular methylation analysis was performed using methylation-specific MLPA (MS-MLPA), which characterized that the deletion of SNURF/SNRPN exon 1 was paternal in origin, consistent with the PWS-like phenotype. Since SNURF/SNRPN gene and the PWS-IC are known to regulate snoRNAs, it is likely that the PWS-like phenotype observed in patients with paternal SNURF/SNRPN deletion is due to the disrupted expression of SNORD116 snoRNAs.
AB - Here we report the smallest deletion involving SNURF/SNRPN that causes major symptoms of Prader-Willi syndrome (PWS), including hypotonia, dysmorphic features, intellectual disability, and obesity. A female patient with the aforementioned and additional features was referred to the Mayo Clinic Cytogenetics laboratory for genetic testing. Chromosomal microarray analysis and subsequent Sanger sequencing identified a de novo 6.4 kb deletion at 15q11.2, containing exon 1 of the SNURF gene and exon 1 of the shortest isoform of the SNRPN gene. SNURF/SNRPN exon 1, which is methylated on the silent maternal allele, is associated with acetylated histones on the expressed paternal allele. This region also overlaps with the PWS-imprinting center (IC). Subsequent molecular methylation analysis was performed using methylation-specific MLPA (MS-MLPA), which characterized that the deletion of SNURF/SNRPN exon 1 was paternal in origin, consistent with the PWS-like phenotype. Since SNURF/SNRPN gene and the PWS-IC are known to regulate snoRNAs, it is likely that the PWS-like phenotype observed in patients with paternal SNURF/SNRPN deletion is due to the disrupted expression of SNORD116 snoRNAs.
KW - Chromosomal microarray
KW - MS-MLPA
KW - PWS-IC
KW - Prader-Willi syndrome
KW - SNURF/SNRPN
UR - http://www.scopus.com/inward/record.url?scp=85019970855&partnerID=8YFLogxK
U2 - 10.1016/j.ejmg.2017.05.003
DO - 10.1016/j.ejmg.2017.05.003
M3 - Article
C2 - 28554868
AN - SCOPUS:85019970855
SN - 1769-7212
VL - 60
SP - 416
EP - 420
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 8
ER -