Mosaic inversion duplication of chromosome 15 without phenotypic effect: Occurrence in a father and daughter

La, Knight; Lipson, Mark; Mann, Joseph D.; Bachman, Ronald

doi:10.1002/ajmg.1320170315

Cited by 22 publications

(11 citation statements)

References 8 publications

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“…The inv dup(15) chromosomes in these individuals were known to be negative for the PWS/AS region by prior fluoresence in situ hybridization (FISH) analysis and uniparental disomy was excluded by previous microsatellite studies. Some of these individuals (the eight JC cases and case DL3, GM04347) have been described in part elsewhere (Knight et al 1984;Crolla et al 1995).…”

Section: Subjectsmentioning

confidence: 98%

Refined molecular characterization of the breakpoints in small inv dup(15) chromosomes

et al. 1996

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Inv dup(15) is the most common supernumerary marker chromosome in humans. To investigate the mechanism responsible for this frequent chromosome rearrangement, we characterized the breakpoints in 18 individuals with small inv dup(15) chromosomes [i.e., negative for the Prader-Willi (PWS)/Angelman syndrome (AS) critical region]. Since two proximal breakpoint regions ("hotspots") for PWS/AS deletions have been previously identified with the most proximal 15q markers D15S541/S542 and S543, we hypothesized that formation of the small inv dup(15) chromosomes may involve one or both of these breakpoint hotspots. By analysis with S542, both breakpoint regions were found to be involved in approximately equal frequencies. In ten cases, the inv dup(15) was negative for S542 (Class I), indicating the breakpoint is between the centromere and the most proximal marker on chromosome 15. For the other eight cases, S542 was positive by fluorescence in situ hybridization (5/5) and/or microsatellite analysis (7/7), but S543 was negative (Class II). These two breakpoint regions appear to be the same as the two proximal breakpoints reported in the common PWS/AS deletions. To initiate cloning and sequencing of the Class II breakpoint, the gap in the yeast artificial chromosome (YAC) contig between S541/S542 and S543 was filled by screening the CEPH YAC and mega-YAC libraries. YACs 705C2 and 368H3 were found to bridge this gap, and therefore contain the more distal breakpoint region. The finding of consistent breakpoints in small inv dup(15), like that found in PWS/AS deletions, provides strong evidence for hotspots for chromosome breakage in this region. In addition, our results show that two extra copies (tetrasomy) of the region from 15cen to the euchromatic region containing S542 are present in individuals with Class II breakpoints. Since most individuals carrying a small inv dup(15) are phenotypically normal, the euchromatin region included in the small inv dup(15) chromosomes does not appear to contain genes with clinically significant dosage effects.

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Section: Subjectsmentioning

confidence: 98%

Refined molecular characterization of the breakpoints in small inv dup(15) chromosomes

et al. 1996

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“…Most such individuals are ascertained through mental and/or developmental retardation (Schreck et al 1977;Wisniewski et al 1979;Maraschio et al 1981); however, reported phenotypes range from normal (Stetten et al 1981;Knight et al 1984) to Prader-Willi (Fujita et al 1980;Wisniewski et al 1980;Ledbetter et al 1982;Robinson et al 1993;Cheng et al 1994;Blennow et al 1995) or Angelman syndrome (Robinson et al 1993;Spinner et al 1995;Buchholz et al 1996) to the inv dup(15) syndrome (Wisniewski et al 1980;Zannotti et al 1980;Plattner et al 1991;Battaglia et al 1997). The inv dup(15) syndrome includes characteristics such as mild, moderate or severe mental and developmental retardation, seizures, autism or autistic traits, abnormal dermatoglyphics and strabismus (Zannotti et al 1980;Plattner et al 1993).…”

Section: Introductionmentioning

confidence: 99%

Isolation and molecular analysis of inv dup(15) and construction of a physical map of a common breakpoint in order to elucidate their mechanism of formation

Wandstrat

Schwartz

2000

Chromosoma

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An inverted duplication of chromosome 15 [inv dup(15)] is the most common supernumerary marker chromosome, comprising approximately 50% of all chromosomes in this class. Structurally, the inv dup(15) is a mirror image with the central axis defining a distal break within either the heterochromatic alpha-satellite array or along the euchromatin in the long (q) arm of the chromosome. There are several types of inv dup(15), classified by the amount of euchromatic material present. Generally, they are bisatellited, pseudodicentric and have a breakpoint in 15q11-q14. A suggested mechanism of formation of inv dup(15) involves illegitimate recombination between homologous chromosomes followed by nondisjunction and centromere inactivation. The proximal portion of chromosome 15 contains several low-copy repeat sequence families and it has been hypothesized that errors in pairing among these repeats may result in structural rearrangements of this chromosome including the inv dup(15). To test this hypothesis and to determine the mechanism of formation, the inv dup(15) from four cases was isolated in somatic cell hybrids and polymerase chain reaction microsatellite markers were used to determine the origin of exchange. Two appeared to result from interchromosomal and two from intrachromosomal exchange, one of which occurred post-recombination. In addition, a detailed physical map of the breakpoint region in the largest inv dup(15) was constructed placing eight new sequence-tagged sites and ten new bacterial artificial chromosome markers in the region.

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“…Reports on individuals with milder phenotypes have been rare. Knight et al [1984] described a 10-year-old girl and her father, both of normal intelligence and with mosaicism for an inv dup(15)(q12) by G banding, but later, FISH studies were performed on the girl, then a 22-year-old woman, revealing a small inv dup(15) without the PWACR [Huang et al, 1997]. Chifari et al [2002] described a 25-year-old woman and an unrelated 27-year-old man, both with mild mental retardation becoming apparent at school age and non-mosaic large inv dup(15).…”

mentioning

confidence: 97%

Healthy 12‐year‐old boy with mosaic inv dup(15)(q13)

Loitzsch

Bartsch²

2006

American J of Med Genetics Pt A

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Mosaic inversion duplication of chromosome 15 without phenotypic effect: Occurrence in a father and daughter

Cited by 22 publications

References 8 publications

Refined molecular characterization of the breakpoints in small inv dup(15) chromosomes

Refined molecular characterization of the breakpoints in small inv dup(15) chromosomes

Isolation and molecular analysis of inv dup(15) and construction of a physical map of a common breakpoint in order to elucidate their mechanism of formation

Healthy 12‐year‐old boy with mosaic inv dup(15)(q13)

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