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Subtelomeric imbalances in phenotypically normal individuals
Author(s) -
Balikova Irina,
Menten Björn,
de Ravel Thomy,
Le Caignec Cédric,
Thienpont Bernard,
Urbina Montse,
DocoFenzy Martine,
de Rademaeker Marjan,
Mortier Geert,
Kooy Frank,
van Den Ende Janneke,
Devriendt Koen,
Fryns JeanPierre,
Speleman Frank,
Vermeesch Joris Robert
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20537
Subject(s) - subtelomere , biology , genetics , phenotype , copy number variation , gene duplication , genetic counseling , gene , chromosome , genome
Subtelomeric imbalances are identified in ∼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. Hum Mutat 28(10), 958–967, 2007. © 2007 Wiley‐Liss, Inc.