A patient with a supernumerary marker chromosome (15), Angelman syndrome, and uniparental disomy resulting from paternal meiosis II non-disjunction
Open Access
- 1 February 2002
- journal article
- research article
- Published by BMJ in Journal of Medical Genetics
- Vol. 39 (2) , 9e-9
- https://doi.org/10.1136/jmg.39.2.e9
Abstract
The chromosome 15 region q11-q13 is imprinted and contains a number of genes that are expressed only from the paternally or the maternally inherited chromosome. This region is also prone to structural rearrangements including interstitial duplications1 and triplications,2 inversions,3 translocations,4 deletions,5 and the formation of supernumerary marker chromosomes (SMCs).6,7 These rearrangements are associated with a wide range of abnormal phenotypes depending upon both the nature of the rearrangement and on the parental origin. For example, Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurobehavioural disorders that are both caused by a deletion of 15q11-q13.5 A deletion on the maternally inherited chromosome 15 gives rise to AS while a paternally inherited deletion causes PWS. These conditions can also be caused by uniparental disomy (UPD) of chromosome 15: maternal UPD cases will be functionally nullisomic for those genes expressed only from a paternally inherited chromosome and gives rise to PWS, while paternal UPD causes AS. Additional copies of the Prader-Willi/Angelman syndrome critical region (PWACR) have also been reported and can occur as familial cases or arise de novo. Unlike deletions, additional copies of the PWACR appear to be associated with an abnormal phenotype only when inherited maternally.8,9 These additional copies can occur as interstitial duplications/triplications or as SMC(15). SMC(15) is the most common marker chromosome observed in man, accounting for 50% of all cases.10 There are two basic types: large SMC(15) extend over most or all of the q11-q13 region, including the PWACR, and are associated with abnormal phenotypes6,11; small SMC(15) do not contain the PWACR and are not generally associated with an abnormal phenotype,11,12 although they have occasionally been shown to occur in association with other disease causing abnormalities such as 15q11-q13 deletions13 …Keywords
This publication has 16 references indexed in Scilit:
- Phenotype–genotype correlation in 20 deletion and 20 non-deletion Angelman syndrome patientsEuropean Journal of Human Genetics, 1999
- Triplication of 15q11-q13 with inv dup(15) in a female with developmental delay.Journal of Medical Genetics, 1998
- Molecular Cytogenetic Evidence for a Common Breakpoint in the Largest Inverted Duplications of Chromosome 15American Journal of Human Genetics, 1998
- Inherited Interstitial Duplications of Proximal 15q: Genotype-Phenotype CorrelationsAmerican Journal of Human Genetics, 1997
- Familial translocations involving 15q11-q13 can give rise to interstitial deletions causing Prader-Willi or Angelman syndrome.Journal of Medical Genetics, 1996
- Supernumerary inv dup(15) in a patient with Angelman syndrome and a deletion of 15q11–q13American Journal of Medical Genetics, 1995
- Angelman syndrome due to paternal uniparental disomy of chromosome 15: A milder phenotype?American Journal of Medical Genetics, 1994
- Uniparental disomy explains the occurrence of the Angelman or Prader-Willi syndrome in patients with an additional small inv dup(15) chromosome.Journal of Medical Genetics, 1993
- Multiplex PCR of three dinucleotide repeats in the Prader-Willi/Angelman critical region (15q11–q13): molecular diagnosis and mechanism of uniparental disomyHuman Molecular Genetics, 1993
- Angelman and Prader‐Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletionAmerican Journal of Medical Genetics, 1989