A 28-kb Deletion Spanning D15S63 (PW71) in Five Families: A Rare Neutral Variant?

• Published in: American journal of human genetics Vol. 65; no. 6; pp. 1588 - 1594
• Main Authors: Buiting, Karin, Dittrich, Bärbel, Dworniczak, Bernd, Lerer, Israela, Abeliovich, Dvorah, Cottrell, Sally, Temple, I. Karen, Harvey, John F., Lich, Christina, Groß, Stephanie, Horsthemke, Bernhard
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01-12-1999; University of Chicago Press; The American Society of Human Genetics
• Subjects: Adolescent; Adult; Angelman syndrome; Angelman Syndrome - diagnosis; Angelman Syndrome - genetics; Base Sequence; Biological and medical sciences; Child; Child, Preschool; Chromosome 15q11–q13; Chromosome Breakage - genetics; Chromosome Deletion; Cloning, Molecular; D15S63; Deletion; DNA Methylation; False Positive Reactions; Female; Genetic Markers - genetics; Genetic Testing; Genetic Variation - genetics; Genomic Imprinting - genetics; Germany; Haplotypes - genetics; Humans; Male; Medical genetics; Medical sciences; Mental and behavioral disorders; Methylation; Pedigree; Physical Chromosome Mapping; Prader-Willi; Prader-Willi Syndrome - diagnosis; Prader-Willi Syndrome - genetics; Germany; Deletion; Prader-Willi; Angelman syndrome; Methylation; D15S63; Chromosome 15q11–q13; Endocrinopathy; Human; Nervous system diseases; False positive; Family study; Genetic variant; Diseases of the osteoarticular system; Exploration; Happy puppet syndrome; Congenital disease; Cerebral disorder; Genetic disease; Genomic imprinting; Gene; Malformation; Chromosome D15; Central nervous system disease; Diagnosis; Mutation; Complex syndrome; Prader Labhart Willi syndrome
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/302670

Methylation analysis with probe PW71 (
D15S63) is an established procedure to test patients suspected of having Prader-Willi syndrome or Angelman syndrome. Using this test, we have identified a 28-kb deletion spanning
D15S63 in five independent families. Sequence analysis revealed identical breakpoints in all the families. The haplotype data are compatible with a common ancestral origin of the deletion in at least two families. The deletion was not found in 1,000 unrelated controls. Although the deletion maps within the imprinting-center region, neither maternal nor paternal inheritance of the deletion appears to affect imprinting in proximal 15q. We conclude that the deletion is a rare neutral variant that can lead to false-positive results in the PW71-methylation test.