Subtelomeric imbalances in phenotypically normal individuals.
Subtelomeric imbalances are identified in approximately 5% of patients with idiopathic mental retardation (MR) and multiple congenital anomalies (MCA). Because of this high incidence, screening for subtelomeric anomalies became part of the routine genetic evaluation of MCA/MR patients. In contrast to the general view that subtelomeric imbalances cause MCA/MR, we report here 15 subtelomeric copy-number changes in 12 families in which the imbalance is inherited from a phenotypically normal parent. We detected inherited deletions at subtelomeres 2q, 3p, 4p, 4q, 6q, 10q, 17p, 17q, Xp, and Yq and duplications at 1q, 4q, 10q, and 11q. Interestingly, in addition to small deletions (<1 Mb) also unexpected large deletions and duplications up to 7.8 Mb were detected. Taken together with previous reports, a total of 16 subtelomeric duplications and 18 deletions inherited from a phenotypically normal parent have now been reported. Clearly, more extensive genotype-phenotype correlations are needed to better understand the phenotypic consequences of these subtelomeric copy number variations and to resolve the current uncertainty for genetic counseling in postnatal and prenatal diagnosis.
Balikova
Irina
I
Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium.
Menten
Björn
B
de Ravel
Thomy
T
Le Caignec
Cédric
C
Thienpont
Bernard
B
Urbina
Montse
M
Doco-Fenzy
Martine
M
de Rademaeker
Marjan
M
Mortier
Geert
G
Kooy
Frank
F
van den Ende
Janneke
J
Devriendt
Koen
K
Fryns
Jean-Pierre
JP
Speleman
Frank
F
Vermeesch
Joris Robert
JR
D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D016615:Telomere / Q000648:ultrastructure*