to the Transmitted Sub-Telomeric Imbalance Collection. This Collection
contains examples of sub-telomeric deletions, duplications and
rearrangements that may have no phenotypic consequences. Further
information about Copy Number Variation (CNV) in sub-telomeric
regions can be found in e.g. the Database of Genomic Variation
(see below) and in the reviews by Balikova et al (Hum Mutat 2007;28:958-967)
and de Vries et al (J Med Genet. 2003 Jun;40:385-398).
This Transmitted Sub-telomeric Imbalance Collection is designed to help Geneticists,
Physicians and families by providing a summary of as many of the known
examples as possible. While every attempt has been made to accurately replicate
details from publications in full or in abstract, no responsibility for
the accuracy of the information or the decisions which might be made in
the light of this Collection can be taken by the compiler who has constructed
the attached Charts.
of the Collection
Like the Chromosome Anomaly Collection, the Transmitted Sub-Telomeric Imbalance
Collection has been sub-divided into three major colour coded groups:
Group I, both parents and children are phenotypically normal.
This cannot, however, guarantee that all other examples with
the same chromosomal breakpoints will necessarily be free of
phenotypic consequences. This is especially true when the extent
of the sub-telomeric imbalances have not been mapped and when
de novo examples of the same abnormality are found. Nevertheless,
two de novo examples without direct transmission have been included
in Group 1 (the del(4)(pterpter) and the derived dup(17)(qterqter)
of Joyce et al, 2001).
Group II, the majority of families are ascertained because of
the phenotype of the proband but parents and/or other family
members with the same sub-telomeric imbalance are unaffected.
The sub-telomeric imbalance may therefore be considered a coincidental
finding in the family concerned.
comparison, Group III consists of directly transmitted subtelomeric
imbalances that have phenotypic consequences in both parents
Transmitted Sub-telomeric Imbalance are illustrated on a chart with arrows
on the Idiograms which indicate the location of each imbalance. Duplications
are on the left hand side and deletions on the right hand side of each chromosome.
Click on the arrow to access the summary chart with further details and click
on the abbreviated reference to obtain the full reference.
Collection concentrates on Transmitted Sub-telomeric Imbalances
detectable with FISH or MLPA and does not include the large amount
of data being generated by array CGH analysis.
should be remembered that phenotypic variability is the hallmark
of many visible and sub-microscopic chromosomal conditions.
working conclusions that arise from this Collection can be summarised
few Group 1 transmitted sub-telomeric imbalances have been ascertained
for incidental reasons and found in a normal parent. This is
most likely to reflect the fact that sub-telomeric testing is
rarely undertaken without significant clinical suspicion of a
visible or sub-microscopic chromosome abnormality.
great majority of sub-telomeric imbalances were Group 2 imbalances
ascertained in an affected child and subsequently found in a
normal parent. These imbalances provide precedents for regions
that may have no phenotypic consequences.
contrast with the Chromosome Anomaly Collection, there were fewer
Group 3 families than Group 2 families but it is not known whether
the parents of Group 2 families are always closely examined by
a Clinician who would be capable of detecting subtle features
of the phenotype present in their affected offspring.
by gathering further examples will it be possible to identify
how much sub-telomeric material can be lost without phenotypic
consequences and identify Sub-Telomeric Imbalances that are consistently
free of phenotypic consequences.
Genetic centres are invited to submit additional examples that may make it
possible to establish whether the phenotypically normal imbalance carriers
represent the benign end of a spectrum of phenotypic effect, or, whether
there are indeed sub-telomeric abnormalities that are consistently free of
phenotypic consequences. A Chromosome Anomaly Collection Submission Form
here or from the compiler.
Other sources of useful information about sub-telomeric chromosome abnormalities
and variants can be found in :
Toronto Database of Genomic Variants (http://projects.tcag.ca/variation/)
the Seattle Structural Variation Database (http://humanparalogy.gs.washington.edu/structuralvariation/).
databases that may contain further examples include:
European Cytogenetic Association Register of Unbalanced Chromosome
Abnormalities which allows on-line registration and to collection
of large numbers of rare cytogenetic and molecular cytogenetic
aberrations at www.ecaruca.net/.
DatabasE of Chromosomal Imbalance and Phenotype in Humans using
Ensemble Resources (DECIPHER) which has been inspired by the
need to distinguish clinically significant imbalances from transmitted
imbalances or polymorphisms detected using micro-arrays. On-line
registration and submission can be carried out at www.sanger.ac.uk/PostGenomics/decipher.
long established UK Association of Clinical Cytogeneticists (ACC)
Chromosome Abnormality Database (CAD) which is on-line for registration
and free searches.
Collection has been compiled by Dr John Barber who can be contacted
Genetics Reference Laboratory (Wessex)
NHS Foundation Trust
Salisbury District Hospital
Tel: +44 (0)1722 429080
Fax: +44 (0)1722 338095
help of Gemma Watkins, Carolyn Wallis, Kelley Gardner and Mac
Gardner in the construction of this entry is gratefully acknowledged.
Viv Maloney kindly constructed the chromosomal idiograms.