Microdeletion and microduplication syndromes Flashcards
(38 cards)
What does microdeletion mean?
Microdeletion (5-10Mb) means only 1 copy of that region is left and haploinsufficiency for dosage sensitive genes results in an abnormal phenotype.
What can cause microdeletions/microduplications?
Caused by Nonallelic Homologous Recombination (NAHR).
What is the difference in phenotype severity between deletions and duplications?
More severe phenotype for deletions than duplications.
What does reduced penetrance mean in the context of microdeletions/microduplications?
Microdeletions/microduplications may be inherited from an unaffected parent, demonstrating reduced penetrance.
What factors influence variable expressivity and reduced penetrance?
- Variable breakpoints
- Differences in genetic background
- Unmasking of recessive variants
- Epigenetic modifications, imprinting
What is Charcot-Marie-Tooth (CMT1A) syndrome caused by?
CMT1A is caused by a reciprocal 1.4Mb duplication encompassing the dosage-sensitive PMP22 gene at 17p11.2.
What characterizes Charcot-Marie-Tooth (CMT1A) syndrome?
CMT1 is characterized by distal muscle weakness, atrophy, sensory loss
What is Smith-Magenis syndrome (SMS) caused by?
SMS is caused by recurrent 3.7Mb deletion/duplications generated by NAHR between LCRs.
What are the characteristic features of Smith-Magenis syndrome (SMS)?
- Distinctive facial features
- Short stature
- Developmental delay
- Cognitive impairment
- Behavioral abnormalities
What is Williams syndrome (WS) characterized by?
- Cardiovascular disease
- Distinctive facies
- Intellectual disability
- Growth abnormalities
What causes Williams syndrome (WS)?
WS is caused by a contiguous gene deletion of the Williams-Beuren syndrome critical region (WBSCR) at 7q11.23.
What is Prader-Willi syndrome (PWS) characterized by?
- Hypotonia
- Obesity
- Developmental delay
- Cognitive impairment
What genetic mechanisms can lead to Prader-Willi syndrome (PWS)?
- Paternal deletion
- Maternal uniparental disomy
- Imprinting defect
What characterizes Angelman syndrome (AS)?
- Severe developmental delay
- Severe speech impairment
- Microcephaly
- Seizures
What is Miller-Dieker syndrome (MDS) characterized by?
MDS is characterized by lissencephaly, microcephaly, and severe mental retardation.
What are the key features of Cri-du-chat syndrome?
- Distinctive cat-like cry
- Severe developmental delay
- Microcephaly
- Low birth weight
- Hypotonia in infancy
- Distinctive facial features
What methods can be used to detect microdeletion/microduplication syndromes?
- Genomic Microarrays
- Fluorescence In Situ Hybridization
- Quantitative Polymerase Chain Reaction
- Multiplex Ligation-Dependent Probe Amplification
- Optical Genome Mapping
True or False: Optical Genome Mapping can detect triploidies.
False
What are CNVs?
Structural variations in the genome involving changes in the number of copies of a particular genomic region, such as deletions and duplications.
What are microarrays commonly used for?
Detection of idiopathic learning difficulties and established or new susceptibility regions associated with developmental delay, intellectual disabilities, and other neurodevelopmental disorders.
What is a disadvantage of CMA?
Balanced rearrangements not detected.
What might not be detected depending on the platform when using CMA?
Triploidy and low level mosaicism.
What is one reason marker chromosomes might be missed?
Depending on the size, marker composition, and coverage of the specific chromosomal region present on the marker.
