title: Scanning for telomeric deletions and duplications and uniparental disomy using genetic markers in 120 children with malformations.
abstract: We screened 120 children with sporadic multiple congenital anomalies and either growth or mental retardation for uniparental disomy (UPD) or subtelomeric deletions. The screening used short tandem repeat polymorphisms (STRP) from the subtelomeric regions of 41 chromosome arms. Uninformative marker results were reanalyzed by using the next available marker on that chromosome arm. In total, approximately 25,000 genotypes were generated and analyzed for this study. Subtelomeric deletions of 1 Mb in size were excluded for 27 of 40 chromosome arms. Among the 120 subjects none was found to have UPD, but five subjects (4%, 95% confidence interval 1-9%) were found to have a deletion or duplication of one or more chromosome arms. We conclude that UPD is not a frequent cause of undiagnosed multiple congenital anomaly syndrome. In addition, we determined that 9p and 7q harbor chromosome length variations in the normal population. We conclude that subtelomeric marker analysis is effective for the detection of subtelomeric duplications and deletions, although it is labor intensive. Given a detection rate that is similar to prior studies and the large workload imposed by STRPs, we conclude that STRPs are an effective, but impractical, approach to the determination of segmental aneusomy given current technology.
authors.affiliation: National Human Genome Research Institute, Genetic Disease Research Branch, 49 Convent Drive, Bethesda, MD 20892, USA. marjr@nhgri.nih.gov
authors.forename: M J
authors.initials: MJ
authors.lastname: Rosenberg
authors.forename: C
authors.initials: C
authors.lastname: Killoran
authors.forename: L
authors.initials: L
authors.lastname: Dziadzio
authors.forename: S
authors.initials: S
authors.lastname: Chang
authors.forename: D L
authors.initials: DL
authors.lastname: Stone
authors.forename: J
authors.initials: J
authors.lastname: Meck
authors.forename: D
authors.initials: D
authors.lastname: Aughton
authors.forename: L M
authors.initials: LM
authors.lastname: Bird
authors.forename: J
authors.initials: J
authors.lastname: Bodurtha
authors.forename: S B
authors.initials: SB
authors.lastname: Cassidy
authors.forename: J M
authors.initials: JM
authors.lastname: Graham
authors.forename: A
authors.initials: A
authors.lastname: Grix
authors.forename: A E
authors.initials: AE
authors.lastname: Guttmacher
authors.forename: L
authors.initials: L
authors.lastname: Hudgins
authors.forename: C
authors.initials: C
authors.lastname: Kozma
authors.forename: R C
authors.initials: RC
authors.lastname: Michaelis
authors.forename: R
authors.initials: R
authors.lastname: Pauli
authors.forename: K F
authors.initials: KF
authors.lastname: Peters
authors.forename: K N
authors.initials: KN
authors.lastname: Rosenbaum
authors.forename: C J
authors.initials: CJ
authors.lastname: Tifft
authors.forename: D
authors.initials: D
authors.lastname: Wargowski
authors.forename: M S
authors.initials: MS
authors.lastname: Williams
authors.forename: L G
authors.initials: LG
authors.lastname: Biesecker
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000782:Aneuploidy; D002648:Child; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D005260:Female; D005819:Genetic Markers; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D020080:Tandem Repeat Sequences; D016615:Telomere / Q000235:genetics*
chemical_list: D005819:Genetic Markers