The Principles of Clinical Cytogenetics - Extra Materials - Springer

172 Kathleen Kaiser-Rogers and Kathleen Rao
Fig. 3. In the example here, the mother (top left) carries a recessive point mutation (asterisk) within a gene
(black box) located on one chromosome homolog (hatched). The father (top right) carries a mutation in the
same gene secondary to interruption via a translocation event. Because the second homolog in each parent
contains a normal allele, both parents are phenotypically normal. This is also true for their first child (bottom
left), who inherited the balanced translocation from her father and the normal hatched chromosome from her
mother. Although their second child (bottom right) is also a balanced translocation carrier, she has inherited
two mutated copies of the gene and therefore manifests the recessive disease. The allele she inherited from her
mother contains a point mutation, whereas the comparable paternally inherited allele has been interrupted secondary
to a translocation.
Phenotypic discrepancies between child and parent could also be explained by the presence of a
recessive allele that is inherited from a chromosomally normal parent. Although the parent is phenotypically
normal because of the presence of a complementary normal allele on the homologous chromosome,
the abnormal allele can be expressed in the offspring, who has no normal allele. The affected
child inherits two mutant alleles; one mutant allele is inherited secondary to the balanced chromosome
rearrangement, whereas the other is inherited from the cytogenetically normal parent (see Fig. 3).
DELETIONS
Autosomal deletions that can be detected by traditional, high-resolution, or molecular cytogenetic
methods produce monosomies that are generally associated with significant pathology. Some exceptions,
however, do exist. Loss of the short arm material from acrocentric chromosomes during the
formation of Robertsonian translocations, for example, has no impact on phenotype. Similarly, the
striking size variation of heterochromatic regions in normal individuals suggests that loss of some, if
not all, of this material is insignificant. There have even been reports of “benign” deletions in regions