Study of 30 patients with unexplained developmental delay and dysmorphic features or congenital abnormalities using conventional cytogenetics and multiplex FISH telomere (M-TEL) integrity assay.
Cryptic subtelomeric chromosome rearrangements are a major cause of mild to severe mental retardation pointing out the necessity of sensitive screening techniques to detect such aberrations among affected patients. In this prospective study a group of 30 patients with unexplained developmental retardation and dysmorphic features or congenital abnormalities were analysed using the recently published multiplex FISH telomere (M-TEL) integrity assay in combination with conventional G-banding analysis. The patients were selected by one or more of the following criteria defined by de Vries et al.: (a) family history with two or more affected individuals, (b) prenatal onset growth retardation, (c) postnatal growth abnormalities, (d) facial dysmorphic features, (e) non-facial dysmorphism and congenital abnormalities. In addition, we included two patients who met these criteria and revealed questionable chromosome regions requiring further clarification. In four patients (13.3%) cryptic chromosome aberrations were successfully determined by the M-TEL integrity assay and in two patients with abnormal chromosome regions intrachromosomal aberrations were characterized by targetted FISH experiments. Our results accentuate the requirement of strict selection criteria prior to patient testing with the M-TEL integrity assay. Another essential precondition is high-quality banding analysis to identify structural abnormal chromosomes. The detection of familial balanced translocation carriers in 50% of the cases emphasizes the significance of such an integrated approach for genetic counselling and prenatal diagnosis.
Deutsches Krebsforschungszentrum, Division of Genetics of Skin Carcinogenesis, Heidelberg, Germany.
Susanne
S
Popp
Birgit
B
Schulze
Martin
M
Granzow
Monika
M
Keller
Heidi
H
Holtgreve-Grez
Brigitte
B
Schoell
Michaela
M
Brough
Hans-Dieter
HD
Hager
Gholamali
G
Tariverdian
Jill
J
Brown
Lyndal
L
Kearney
Anna
A
Jauch
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology; D005260:Female; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016615:Telomere / Q000235:genetics*; D014178:Translocation, Genetic