Molecular analysis of ring chromosome 20 syndrome reveals two distinct groups of patients.
BACKGROUND
The ring chromosome 20 syndrome (R20) is a rare genetic disorder associated with a refractory electroclinical epilepsy syndrome and variably expressed comorbidities of intellectual disability and dysmorphism.


METHODS
To understand the structure and composition of the ring chromosome 20 (r(20)) in this patient cohort, blood specimens from 28 affected individuals were analysed by cytogenetic, fluorescence in situ hybridisation, and/or high resolution whole genome single nucleotide polymorphism array analysis.


RESULTS
These studies revealed two distinct groups of patients. Group 1 (N=21) was mosaic for the r(20) and a normal cell line with no detectable deletions or duplications of chromosome 20 in either cell line. The mosaic nature of these rings suggests a postzygotic origin with formation of the ring by fusion of the telomeric regions with no apparent loss of subtelomeric or telomeric DNA. Group 2 (N=7) had non-mosaic ring chromosomes with a deletion at one or both ends of the chromosome, near the ring fusion point. The non-mosaic nature of these rings is consistent with a meiotic origin. The age of onset of seizures was significantly lower in the non-mosaic patients (group 2, median age of onset 2.1 years) than in the mosaic patients (group 1, median age of onset 6.0 years). Patients from group 2 had more extensive comorbidities.


CONCLUSIONS
These studies demonstrate that r(20) is molecularly heterogeneous and formed by two distinct mechanisms, which, in turn, produce different phenotypic spectrums.
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, 19104, USA.
Laura K
LK
Conlin
Whitney
W
Kramer
Anne L
AL
Hutchinson
Xia
X
Li
Harold
H
Riethman
Hakon
H
Hakonarson
John C
JC
Mulley
Ingrid E
IE
Scheffer
Samuel F
SF
Berkovic
Syed A
SA
Hosain
Nancy B
NB
Spinner
D017668:Age of Onset; D002478:Cells, Cultured; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012303:Ring Chromosomes; D012640:Seizures / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D013577:Syndrome