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How microsatellite analysis can be exploited for subtelomeric chromosomal rearrangement analysis in mental retardation
  1. EUGENIA BORGIONE*,
  2. MARIANGELA LO GIUDICE*,
  3. ORNELLA GALESI*,
  4. LUCIA CASTIGLIA*,
  5. PINELLA FAILLA,
  6. CORRADO ROMANO,
  7. ANGELA RAGUSA*,
  8. MARCO FICHERA*
  1. *Laboratorio di Patologia Genetica, IRCCS Oasi Maria SS, Via Conte Ruggero 73, 94018 Troina (Enna), Italy
  2. †Unità Operativa di Pediatria, IRCCS Oasi Maria SS, Troina, Italy
  1. Dr Fichera, mfichera{at}oasi.en.it

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Editor—The genetic causes of mental retardation are still largely unknown so that about 34% of cases of severe to moderate and 80% of mild mental retardation remain unresolved.1 ,2 Consequently, genetic counselling is difficult in these cases. Chromosomal rearrangements are still the most frequent cause of mental retardation and cytogenetic analysis at 400-550 band resolution cannot detect rearrangements smaller than 5 Mb. Therefore, any new technologies to improve cytogenetic analysis would be of great benefit. In recent years, there has been evidence that the cause of 6-7% of mental retardation involves subtle chromosome rearrangements.

Several molecular methodologies have been used successfully to investigate the integrity of telomeres, such as hypervariable polymorphisms (HVPs), FISH, and CGH, while others based on DNA array approaches are being developed.2 The choice of method rests on considerations of feasibility, cost, reproducibility, and sensitivity. FISH and microsatellite analyses are the techniques most commonly used by numerous laboratories and both of them are still being evaluated in terms of their performance and practicability. FISH based analysis with telomeric specific probes provides a simultaneous investigation of all chromosomes ends, resulting in total detection of chromosome rearrangements without requiring the examination of parental chromosomes.3-5 However, this method does not assign parental origin, it loses UPD events, and only gives information regarding abnormalities spanning the probe's DNA region. Although now simplified by being available in kit form, the method not only requires considerable expertise in molecular cytogenetics, but is also expensive and time consuming.

HVP analysis using microsatellites, which is both easy and inexpensive, has two main problems, as it requires both parental DNA samples and high informativeness, established by the number and frequencies of alleles. However, even for highly heterozygous loci ≅0.8, the detection rate for monosomy and trisomy is 0.64 and 0.5, …

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