TY - JOUR
T1 - Prospective screening for subtelomeric rearrangements in children with mental retardation of unknown aetiology: the Amsterdam experience
AU - van Karnebeek, C.D.
AU - Koevoets, C.
AU - Sluijter, S.
AU - Bijlsma, E.K.
AU - Smeets, D.F.C.M.
AU - Redeker, E.J.W.
AU - Hennekam, R.C.M.
AU - Hoovers, J.M.N.
AU - Smeets, D. F. M. C.
PY - 2002
Y1 - 2002
N2 - Objective: The frequency of subtelomeric rearrangements in patients with unexplained mental retardation (MR) is uncertain, as most studies have been retrospective and case retrieval may have been biased towards cases more likely to have a chromosome anomaly. To ascertain the frequency of cytogenetic anomalies, including subtelomeric rearrangements, we prospectively screened a consecutive cohort of cases with unexplained MR in an academic tertiary centre. Methods: Inclusion criteria were: age <18 years at referral, IQ <85, no aetiological diagnosis after complete examination, which included karyotyping with high resolution banding (HRB). Results: In 266 karyotyped children, anomalies were detected in 20 (7.5%, seven numerical, 13 structural); 39 cases were analysed by FISH for specific interstitial microdeletions, and anomalies were found in nine (23%). FISH analyses for subtelomeric microdeletions were performed in 184 children (44% moderate-profound MR, 51% familial MR), and one rearrangement (0.5%) was identified in a non-familial MR female with mild MR (de novo deletion 12q24.33-qter). The number of probable polymorphisms was considerable: 2qter (n=7), Xpter (n=3), and Ypter (n=1). A significantly higher total number of malformations and minor anomalies was present in the cytogenetic anomaly group compared to the group without cytogenetic anomalies. Conclusions: The total frequency of cytogenetic anomalies in this prospective study was high (1 :10), but the frequency of subtelomeric rearrangements was low. The most likely explanations are the high quality of HRB cytogenetic studies and the lack of clinical selection bias. Conventional cytogenetic analyses, combined with targeted microdeletion testing, remain the single most effective way of additional investigation in mentally retarded children, also in a tertiary centre
AB - Objective: The frequency of subtelomeric rearrangements in patients with unexplained mental retardation (MR) is uncertain, as most studies have been retrospective and case retrieval may have been biased towards cases more likely to have a chromosome anomaly. To ascertain the frequency of cytogenetic anomalies, including subtelomeric rearrangements, we prospectively screened a consecutive cohort of cases with unexplained MR in an academic tertiary centre. Methods: Inclusion criteria were: age <18 years at referral, IQ <85, no aetiological diagnosis after complete examination, which included karyotyping with high resolution banding (HRB). Results: In 266 karyotyped children, anomalies were detected in 20 (7.5%, seven numerical, 13 structural); 39 cases were analysed by FISH for specific interstitial microdeletions, and anomalies were found in nine (23%). FISH analyses for subtelomeric microdeletions were performed in 184 children (44% moderate-profound MR, 51% familial MR), and one rearrangement (0.5%) was identified in a non-familial MR female with mild MR (de novo deletion 12q24.33-qter). The number of probable polymorphisms was considerable: 2qter (n=7), Xpter (n=3), and Ypter (n=1). A significantly higher total number of malformations and minor anomalies was present in the cytogenetic anomaly group compared to the group without cytogenetic anomalies. Conclusions: The total frequency of cytogenetic anomalies in this prospective study was high (1 :10), but the frequency of subtelomeric rearrangements was low. The most likely explanations are the high quality of HRB cytogenetic studies and the lack of clinical selection bias. Conventional cytogenetic analyses, combined with targeted microdeletion testing, remain the single most effective way of additional investigation in mentally retarded children, also in a tertiary centre
KW - AMC wi-eigen
U2 - https://doi.org/10.1136/jmg.39.8.546
DO - https://doi.org/10.1136/jmg.39.8.546
M3 - Article
C2 - 12161591
SN - 0022-2593
VL - 39
SP - 546
EP - 553
JO - Journal of medical genetics
JF - Journal of medical genetics
IS - 8
ER -