Cytogenetic Imbalances (2) Flashcards
Name 4 macro deletion syndromes
1) cri-du-chat
2) wolf hirschorn syndrome
3) miller-dieker syndrome
4) smith magenis syndrome
Cause of Cri-du-chat, what is the critical region?
Del 5p
Critical region = 5p15.3-5p15.2
Features of cri- du-chat?
Cat like cry.
Microcephaly
Poor muscle tone
MR
Cause of wolf hirschorn syndrome?
Del 4p
Features of wolf-hirschorn syndrome
Prominent forehead
Wide set eyes
Broad beaked nose
GREEK WARRIOR HELMET
Cause of miller dieker syndrome?
Del(17)(p13.3) terminal deletion of 17p
Deletion of LIS1
Features of miller dieker syndrome?
Lissencephaly
Seizures
Cause of smith Magenis syndrome?
Del(17)(p11.2p11.2)
Interstitial deletion of proximal 17p (4mb common deletion region)
Features of smith magenis syndrome?
Behavioural problems - self harming and sleep problems
Square face, deep set eyes, full cheeks UNIBROW (synophrys)
What is NAHR?
Non-allelic homologous recombination between regions of homologous interspersed throughout the genome
Highly polymorphic regions of low copy repeats
Two LCRs close to each other can result in deletion or duplication of the intervening sequence
Name two microdeletion syndromes and a common cause for microdeletion syndromes
DiGeorge syndrome
Williams beuren syndrome
Cause of digeorge syndrome?
Dell 22(q11.2q11.2)
Features of digeorge
Aortic arch defects
Learning difficulties
Hypercalcaemia
*can be inherited from phenotypically normal parent
Cause of Williams-beuren syndrome
Del(7)(q11.23q11.23)
Features of Williams beuren syndrome
Heart defects Elfin-like features Cocktail party manner LD (can be talented musicians) Hypercalcaemia (opposite to degeorge)
What are the possible results of segregation of a balanced reciprocal translocation?
1) alternate segregation- normal/balanced products
2) adjacent segregation = unbalanced products as a result of 2:2
3) tertiary or interchange = unbalanced products as a result of 3:1
What is tertiary trisomy? Great be an example
3rd chromosome made up of two chromosomes
Emanuel syndrome: 47,XX, +der(22)t(11;22)
What common translocation causes Emanuel syndrome?
T(11;22)(q23;q11)
Unbalanced child has gain of 22pter-22q11 and 11q23-11qter in der(22)t(11;22)
What is the recurrence rate of Emanuel syndrome to a balanced female carrier? What are risks to female carriers?
Recurrance 5-6%
Increased risk of pregnancy loss
Features of Emmanuel syndrome?
MR Craniofacial abnormalities Deep set eyes Lower set ears Longer upper lip Congenital heart defects
What can cause a viable adjacent 1 segregation?
T(4;8) (p16;23) recurrent reciprocal segregation
46,xx, der(4) t(4;8) gives a wolf hirschorn phenotype (missing 4p and gained 8p)
46,xx,der(8)t(4;8)- less specific features
Name of an inversion including the centromere?
Pericentric
Inversion excluding the centromere?
Paracentric
What types of inversions have a higher risk f having abnormal children?
Big inversions
Pericentric
End sections are very small
What pericentric inversions have the highest risk of having child with LD?
Ones where non inverted segments are small or non-coding (i.e. Acrocentric short arms)
What are possible results of meiotic loop at meiosis with a pericentric inversion?
1) normal chromsome
2) inverted chromosome
3) recombinant chromosome dup p distal
4) recombinant chromosome dup q distal
What are results of meiotic loop for paracentric inversions?
Normal
Inverted
Dicentric recombinant chromosome- most likely lost
Acentric recombinant chromosome- mostly lost
What is it called when one chromosome is inserted into another?
Interchromosomal insertion (3 break points)
What is it called when a segment of one chromosome is inserted into dif place of same chromosome ?
Intrachromosomal insertion
How is a ring chromosome formed?
Formed from a single chromosome with loss of material and fusion of the p and q arms
True or false: less material is lost with large ring chromosomes
True- usually in place of normal chromosome
What is dynamic mosaicism?
Frequent errors at mitotic division eg. Rings
- loss of the ring
- additional copies
- double size
Features of generalised ring chromosome syndrome (large ring replacing chromosome)
Growth restriction/ short stature
What does c-banding do?
Stains constitutive heterochromatin (non coding genetic material) dark - use to establish significance of marker
What does silver staining do?
Uses silver nitrate- results in a dark deposit corresponding to satellite stalks of Acrocentric chromosomes- if marker pos then made from Acrocentric chromosome and is non coding
Resolution of karyotyping and fish?
G banding 3-5 me
Fish 100s kb
Cons of arrays
Only detects genetic imbalance
Not imprinting
No positional information
Mosaics may not be detected
Pros of array
High resolution
Genome wide
Does not require viable tissue or cell culture
