title: Different distribution of the genetic subtypes of the Prader-Willi syndrome in the elderly.
abstract: The Prader-Willi syndrome (PWS) is a genetic disorder caused by the absent expression of the paternal copy of maternally imprinted genes in chromosome region 15q11-13. The frequencies of different subtypes in PWS are usually given in literature as 70% deletion, 25-30% maternal uniparental disomy (mUPD) and 3-5% others (imprinting centre (IC) defects and translocations). Little is known about factors that influence the frequency of genetic subtypes in PWS. The study sample comprised 102 adults with clinically and genetically confirmed PWS, contacted through the Dutch Prader-Willi Parent Association and through physicians specialized in treating persons with intellectual disabilities. Genetic testing showed 55 persons (54%) with a paternal deletion, 44 persons (43%) with an mUPD and 3 persons (3%) with a defect of the IC. The observed distribution in our study differed from that in literature (70% deletion, 30% mUPD), which was statistically significant (z-score: P<0.05). This was mainly caused by a higher proportion of mUPD in the advanced age groups. Differences in maternal age and BMI of persons with PWS could not explain the differences in distribution across the age groups. Our study population had a much broader age range, compared with other studies, because of a predominance of elderly people (40+ years) with PWS. In other studies, these elderly persons might have been undiagnosed and/or underreported because of a lack of genetic diagnosis. The results underline both the need for correct genetic diagnosis in all persons with PWS and adjustment of the guidelines for preventive management in adulthood.
authors.affiliation: Department of Clinical Genetics, Maastricht UMC, Maastricht, The Netherlands. margje.sinnema@gen.unimaas.nl
authors.forename: Margje
authors.initials: M
authors.lastname: Sinnema
authors.forename: Kees E P
authors.initials: KE
authors.lastname: van Roozendaal
authors.forename: Marian A
authors.initials: MA
authors.lastname: Maaskant
authors.forename: Hubert J M
authors.initials: HJ
authors.lastname: Smeets
authors.forename: John J M
authors.initials: JJ
authors.lastname: Engelen
authors.forename: Nieke
authors.initials: N
authors.lastname: Jonker-Houben
authors.forename: Constance T R M
authors.initials: CT
authors.lastname: Schrander-Stumpel
authors.forename: Leopold M G
authors.initials: LM
authors.lastname: Curfs
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005820:Genetic Testing; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011218:Prader-Willi Syndrome / Q000235:genetics*
references.citation: Curr Opin Obstet Gynecol. 2009 Jun;21(3):260-4
references.pmid: 19276804
references.citation: Am J Med Genet A. 2004 Jun 15;127A(3):238-43
references.pmid: 15150773
references.citation: Eur J Hum Genet. 2009 Jan;17(1):3-13
references.pmid: 18781185
references.citation: Eur J Hum Genet. 2007 Jan;15(1):127-30
references.pmid: 16957680
references.citation: N Engl J Med. 1981 Feb 5;304(6):325-9
references.pmid: 7442771
references.citation: Obesity (Silver Spring). 2006 Jun;14(6):1028-37
references.pmid: 16861608
references.citation: Dev Med Child Neurol. 1995 Dec;37(12):1101-9
references.pmid: 8566468
references.citation: Am J Med Genet A. 2004 Feb 1;124A(4):333-8
references.pmid: 14735579
references.citation: Eur J Hum Genet. 2004 Mar;12(3):238-40
references.pmid: 14679397
references.citation: Arch Gen Psychiatry. 2007 Oct;64(10):1123-31
references.pmid: 17909124
references.citation: Am J Med Genet. 1997 Feb 11;68(4):433-40
references.pmid: 9021017
references.citation: J Intellect Disabil Res. 2002 Jan;46(Pt 1):41-50
references.pmid: 11851855
references.citation: J Hum Genet. 2007;52(4):297-307
references.pmid: 17262171
references.citation: Arch Dis Child. 2003 Mar;88(3):263-4
references.pmid: 12598399
references.citation: Nat Genet. 2008 Jun;40(6):719-21
references.pmid: 18500341
references.citation: Nature. 1989 Nov 16;342(6247):281-5
references.pmid: 2812027
references.citation: Fertil Steril. 2009 Feb;91(2):305-15
references.pmid: 19201275
references.citation: J Med Genet. 2001 Nov;38(11):792-8
references.pmid: 11732491
references.citation: J Clin Endocrinol Metab. 2008 Nov;93(11):4183-97
references.pmid: 18697869
references.citation: Am J Med Genet A. 2007 Mar 1;143A(5):430-42
references.pmid: 17236194
references.citation: Pediatrics. 1993 Feb;91(2):398-402
references.pmid: 8424017
references.citation: J Med Genet. 2003 May;40(5):e63
references.pmid: 12746417
references.citation: Lancet. 2002 Jan 12;359(9301):135-6
references.pmid: 11809260
references.citation: Am J Med Genet. 2001 Jan 8;105(1):71-5
references.pmid: 11425004
references.citation: Nat Genet. 1995 Apr;9(4):395-400
references.pmid: 7795645
references.citation: Am J Ment Retard. 2006 May;111(3):193-8
references.pmid: 16597186
references.citation: Am J Med Genet. 1994 May 15;51(1):35-40
references.pmid: 8030667
references.citation: J Med Genet. 1997 Nov;34(11):917-23
references.pmid: 9391886
references.citation: Am J Med Genet. 2000 Dec 18;95(5):454-60
references.pmid: 11146466