Molecular cytogenetic characterisation of a novelde novoring chromosome 6 involving a terminal 6p deletion and terminal 6q duplication in the different arms of the same chromosome.
BACKGROUND
Ring chromosome 6 is a rare sporadic chromosomal abnormality, associated with extreme variability in clinical phenotypes. Most ring chromosomes are known to have deletions on one or both chromosomal arms. Here, we report an atypical and unique ring chromosome 6 involving both a distal deletion and a distal duplication on the different arms of the same chromosome.


METHODS
In a patient with intellectual disability, short stature, microcephaly, facial dysmorphology, congenital heart defects and renovascular disease, a ring chromosome 6 was characterised using array-CGH and dual-colour FISH. Thede-novoring chromosome 6 involved a 1.8 Mb terminal deletion in the distal short arm and a 2.5 Mb duplication in the distal long arm of the same chromosome 6. This results in monosomy for the region 6pter to 6p25.3 and trisomy for the region 6q27 to 6qter. Analysis of genes in these chromosomal regions suggests that haploinsufficiency forFOXC1andGMDSgenes accounts for the cardiac and neurodevelopmental phenotypes in the proband. The ring chromosome 6 reported here is atypical as it involves a unique duplication of the distal long arm. Furthermore, the presence of renovascular disease is also a unique feature identified in this patient.


CONCLUSIONS
To the best of our knowledge, a comparable ring chromosome 6 involving both a distal deletion and duplication on different arms has not been previously reported. The renovascular disease identified in this patient may be a direct consequence of the described chromosome rearrangement or a late clinical presentation in r(6) cases. This clinical finding may further support the implicated role ofFOXC1gene in renal pathology.
Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
Nikolai Paul
NP
Pace
Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, UK.
Frideriki
F
Maggouta
Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, UK.
Melissa
M
Twigden
Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.|Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.|Department of Pathology, Medical Genetics Unit, Mater Dei Hospital, Msida, Malta.
Isabella
0000-0003-0639-3055
I
Borg
Dysmorphology; FOXC1 gene; Molecular cytogenetics; Renovascular disease; Ring chromosome 6