Welcome 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).

Disclaimer
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.

Structure of the Collection
Like the Chromosome Anomaly Collection, the Transmitted Sub-Telomeric Imbalance Collection has been sub-divided into three major colour coded groups:

In 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).

In 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.

For comparison, Group III consists of directly transmitted subtelomeric imbalances that have phenotypic consequences in both parents and children.

Accessing the Collection
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.

Notes:
This 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.

It should be remembered that phenotypic variability is the hallmark of many visible and sub-microscopic chromosomal conditions.

The working conclusions that arise from this Collection can be summarised as:

Very 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.

The 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.

By 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.

Only 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.

Contribute data:
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 is available here or from the compiler.

Links:
Other sources of useful information about sub-telomeric chromosome abnormalities and variants can be found in :

The Toronto Database of Genomic Variants (http://projects.tcag.ca/variation/)

and the Seattle Structural Variation Database (http://humanparalogy.gs.washington.edu/structuralvariation/).

Other databases that may contain further examples include:

The 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/.

The 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.

The long established UK Association of Clinical Cytogeneticists (ACC) Chromosome Abnormality Database (CAD) which is on-line for registration and free searches.

This Collection has been compiled by Dr John Barber who can be contacted at:

National Genetics Reference Laboratory (Wessex)

Salisbury NHS Foundation Trust
Salisbury District Hospital
Salisbury
SP2 8BJ

UK
Tel: +44 (0)1722 429080
Fax: +44 (0)1722 338095
e-mail: john.barber@salisbury.nhs.uk

Acknowledgements

The 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.