Dr. R. Jazayeri Alborz University of Medical Sciences

Structural abnormalitis  Structural chromosome rearrangements result from chromosome breakage with subsequent reunion in a different configuration.  They can be balanced or unbalanced.  In balanced rearrangements the chromosome complement is complete, with no loss or gain of genetic material. Balanced rearrangements are generally harmless with the exception of rare cases in which one of the breakpoints damages an important functional gene. However, carriers of balanced rearrangements are often at risk of producing children with an unbalanced chromosomal complement.  The Unbalanced chromosomal rearrangment, contains an incorrect amount of chromosome material and the clinical effects are usually serious.

 Balanced chromosomal rearrangements: Reciprocal translocations Robertsonian translocations Inversions  Unbalanced chromosomal anomalies: Deletions & Duplications Structural abnormalitis

M. Houshmand

Translocation Translocation is the transfer of chromosomal material between chromosomes. The process requires breakage of both chromosomes with repair in an abnormal arrangement.  Three types of translocation are recognized: Reciprocal Robertsonian (centric fusion) Insertional

Reciprocal translocation  Reciprocal translocation involves breakage of at least two non-homologous chromosomes with exchange of the fragments, either the long or the short arm may break, any pair of chromosomes may be involved, usually the chromosome number remains at 46, the carrier of this translocation is called a balanced carrier.

Reciprocal translocation Balanced exchange of genetic material between chromosomes Can result in unbalanced gametes  recurrent miscarriage  fetal abnormality  liveborn with structural defects + dysmorphism + MR

Reciprocal translocation NormalBalancedDup/del Normal Balanced translocation

Robertsonian translocation Robertsonian translocation results from breakage of two acrocentric chromosomes at or close to their centromeres, with subsequent fusion of their long arms, this also referred as Centric Fusion. The short arms of each chromosome are lost. The total chromosome number is reduced to 45.

Balanced Rearrangements ReciprocaI translocations Robertsonian translocation

rob(14q21q) 

rob(14q21q) gametogenesis

The rob(14q21q) is the most important Robertsonian translocation in terms of its frequency (8%) and genetic risk. Most familial translocation DS is due to the rob(14q21q). There is 1/3 risk for having a DS child, in theory.  The risk of having a liveborn child with translocation DS is a little less (around 10% for maternal, 1-3% for paternal rob translocation). This likely reflects the loss, through spontaneous abortion. rob(14q21q)

Insertion M. Houshmand

Inversion Inversions arise from two chromosomal breaks within a single chromosome, with inversion through 180° of the segment between the breaks. If both breaks are in a single arm and the centromere in not involved, it is termed Paracentric Inversion. which is difficult to detect and unlikely to give viable offspring. If both breaks are on either side of the centromere, it is termed Pericentric Inversion.

 If the inverted segment includes the centromere, the inversion is pericentric. The pericentric inversion has one break in the short arm and one in the long arm The cytogenetic nomenclature: 46,XX,inv(3)(p25q21) Pericentric inversion

Pericentric Inversion

 If the inverted segment does not include the centromere, it is paracentric. In the paracentric inversion both breaks occur in the same arm. The cytogenetic nomenclature: 46,XY,inv(11)(q21q23) Paracentric inversion

Deletion Involves loss of part of a chromosome. results in monosomy for that segment of the chromosome.  Deletions are recognized as existing at two levels: A 'large‘ chromosomal deletion can be visualized under the microscope. Submicroscopic microdeletions have been identified with the help of high- resolution prometaphase cytogenetics

Deletion M. Houshmand

Duplication  Duplication: an additional copy of segment of a chromosome is present.  Duplications are more common than deletions and generally less harmful.

Duplication

Ring Chromosome Ring chromosome is formed when a break occurs on each arm of a chromosome leaving two sticky ends which reunite as a ring. The terminal ends are lost. Often causes growth failure and mental handicap.

Ring Chromosome

Isochromosome Isochromosome is an abnormal chromosome which has deletion of one arm with duplication of the other. The most commonly encountered isochromosome is that made up ot two long arms of the X which accounts for approximately 15% of Turner’s syndrome.

Isochromosome

Chromosome Analysis Indications 1. Multiple congenital aabnormalities 2. Unexplained mental retardation 3. Sexual ambiguity or abnormality in sexual development 4. Infertility 5. Recurrent miscarriage 6. Unexplained stillbirth 7. Malignancy 8. Chromosome breakage syndromes