Cri-du-Chat Syndrome Cytogenetically Cryptic Recombination Aneusomy of Chromosome 5: Implications in Recurrence Risk
1Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
Molecular Syndromology
|November 4, 2010
Summary
Cri-du-chat syndrome, a genetic disorder, can arise from a 5p deletion and 5q duplication. Molecular analysis is crucial for identifying this rare condition and assessing recurrence risk.
Area of Science:
- Genetics
- Molecular Biology
- Clinical Genetics
Background:
- Cri-du-chat syndrome results from haploinsufficiency of genes on chromosome 5p.
- Typically caused by sporadic deletions with low recurrence risk.
- Rarely, 5p monosomy is accompanied by 5q trisomy, often linked to parental pericentric inversions.
Observation:
- A patient presented with cri-du-chat syndrome phenotype but a normal G-banding karyotype.
- Molecular analyses (MLPA and array CGH) detected a 5p deletion and 5q duplication.
- Parental testing revealed a large pericentric inversion with breakpoints at 5p15.31 and 5q35.1.
Findings:
- Identified a cryptic 5p deletion and 5q duplication in a cri-du-chat syndrome patient with a normal karyotype.
- Demonstrated the association between this specific chromosomal anomaly and a parental pericentric inversion.
- Confirmed the utility of advanced molecular techniques for diagnosing complex chromosomal rearrangements.
Implications:
- Highlights the importance of molecular cytogenetics in diagnosing subtle chromosomal abnormalities.
- Establishes a high recurrence risk for families with such parental inversions.
- Provides critical information for genetic counseling regarding reproductive options.
Related Concept Videos
01:17Karyotyping
Describing the number and physical features of chromosomes can reveal abnormalities that underlie genetic diseases. This description is facilitated by special staining techniques that produce a particular banding pattern on each chromosome. State-of-the-art techniques make this approach even more powerful, enabling the detection of individual genes that cause disease.A Simple Chromosome Staining Technique Provides Valuable Scientific InsightSome genetic diseases can be detected by looking at...
01:29Nondisjunction
During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.
01:21Nondisjunction
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold sister...
02:08Gene Conversion
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
01:39Chromosomal Theory of Inheritance
In 1866, Gregor Mendel published the results of his pea plant breeding experiments, providing evidence for predictable patterns in the inheritance of physical characteristics. The significance of his findings was not immediately recognized. In fact, the existence of genes was unknown at the time. Mendel referred to hereditary units as “factors.”
01:58X-Inactivation
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.