Micro-array analyses decipher exceptional complex familial chromosomal rearrangement
- 3 January 2006
- journal article
- case report
- Published by Springer Nature in Human Genetics
- Vol. 119 (1-2) , 145-153
- https://doi.org/10.1007/s00439-005-0103-z
Abstract
Recently there has been an increased interest in large-scale genomic variation and clinically in the consequences of haploinsufficiency of genomic segments or disruption of normal gene function by chromosome rearrangements. Here, we present an extraordinary case in which both mother and daughter presented with unexpected chromosomal rearrangement complexity, which we characterized with array-CGH, array painting and multicolor large insert clone hybridizations. We found the same 12 breakpoints involving four chromosomes in both mother and daughter. In addition, the daughter inherited a microdeletion from her father. We mapped all breakpoints to the resolution level of breakpoint spanning clones. Genes were found within 7 of the 12 breakpoint regions, some of which were disrupted by the chromosome rearrangement. One of the rearrangements disrupted a locus, which has been discussed as a quantitative trait locus for fetal hemoglobin expression in adults. Interestingly, both mother and daughter show persistent fetal hemoglobin levels. We detail the most complicated familial complex chromosomal rearrangement reported to date and thus an extreme example of inheritance of chromosomal rearrangements without error in meiotic segregation.Keywords
This publication has 23 references indexed in Scilit:
- Loss-of-function mutation of the AF9/MLLT3 gene in a girl with neuromotor development delay, cerebellar ataxia, and epilepsyHuman Genetics, 2005
- The complex nature of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypesJournal of Medical Genetics, 2005
- Array painting: a method for the rapid analysis of aberrant chromosomes using DNA microarraysJournal of Medical Genetics, 2003
- Ten years follow up of a boy with a complex chromosomal rearrangement: Going from a > 5 to 15‐breakpoint CCRAmerican Journal of Medical Genetics Part A, 2002
- An Optimized Probe Set for the Detection of Small Interchromosomal Aberrations by Use of 24-Color FISHAmerican Journal of Human Genetics, 2000
- A de novo complex chromosomal rearrangement with nine breakpoints characterised by FISH in a boy with mild mental retardation, developmental delay, short stature and microcephalyClinical Genetics, 1999
- A new approach to the elucidation of complex chromosome rearrangements illustrated by a case of Rieger syndrome.Journal of Medical Genetics, 1998
- Balanced complex chromosome rearrangement ascertained through prenatal diagnosisAmerican Journal of Medical Genetics, 1994
- Complex de novo rearrangement involving four chromosomes and ten break points with interstitial deletions and duplicationAmerican Journal of Medical Genetics, 1988
- Hereditary persistence of fetal haemoglobin (HPFH) in conjunction with a chromosomal translocation involving the haemoglobin β locusBritish Journal of Haematology, 1984