The end of the beginning of chromosome ends†

A 2.3 Mb duplication of chromosome 8q24.3 associated with severe mental retardation and epilepsy detected by standard karyotype

“…In the last few years, a general consensus has been reached on the fact that the more closely chromosomes are studied, the lower is the chance of finding a rearrangement with the molecular test; 33 in everyday practice, rearrangements of 5 -10 Mb or even larger are easily missed. 33,34 Thus, it is rather astonishing that our 8q duplication was suspected on 400 G-band karyotypes. We might hypothesize that the chromatin status of the duplicated distal 2.3 Mb 8q is less compact than the rest of the metaphasic chromosome, as if the duplication had induced an epigenetic decondensation of the chromatin at least in lymphocytes.…”

Clinical Genetic Evaluation of the Child With Mental Retardation or Developmental Delays

“…[37][38][39][40][41][42][43][44] Since a complete set of FISH probes has become available clinically, the utility of these probes has been demonstrated by the numerous reports of patients with mental retardation who have had a previously normal routine karyotype, suggesting that subtelomeric abnormalities (deletions or duplications of chromosome regions) are second only to Down syndrome as the most common cause of mental retardation. 41,45 Some deletions and duplications of clinically significant chromosome material at the telomeres are not visible by standard karyotype analytic techniques; these are often referred to as "cryptic" subtelomeric chromosome anomalies (ie, they are not detectable by routine cytogenetic testing). The newer FISH techniques have allowed more sensitive analysis of the telomeres for clinically significant abnormalities.…”

“…Also, 0.5% of children with mild mental retardation of previously unknown etiology have been found to have cryptic telomere rearrangements as the etiology. 41,45 Only a few subtelomeric syndromes have been delineated to date (Table 4).…”

“…Biesecker 45 reviewed 14 studies involving 1718 subjects who were selected on the basis of mental retardation, growth retardation, major and minor anomalies, exclusion of known diagnosis, and familial versus sporadic occurrence. It is notable that even with the variation in subject selection criteria from study to study, there was a relatively constant yield of subtelomere abnormalities detected by FISH of approximately 6%.…”

Detection of chromosomal imbalances using combined MLPA kits in patients with syndromic intellectual disability

“…Previously reported studies that performed subtelomere analysis showed an overall abnormality rate of 6%, varying between different studies from 2 to 29% (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The reasons for these differences are the inclusion criteria and the assay used in the study, the size of the cohort and the complete exclusion (or not) of the polymorphisms.…”