materials that are suitable for chromosome analysis
dividing cells; arrested in metaphase
tissues: blood, skin fibroblasts or fetal tissue
2 important chemicals in workflow of chromosome analysis
phytohemagglutinin = poison -> initiate proliferation of T-lymphocytes
colchicine -> cells in mitosis get arrested in metaphase
Karyotype - types of banding
G-banding
Q-banding
R-banding
Chromosome aberrations - formula
chromosome count, gonosomes, aberrations(s)
if patient has several aberrations -> start with gonosomes
autosomes in ascending order from 1 to 22
q: long arm
p: short arm
; inbetween break points
Number of chromosomes
Indications for chromosome analysis in children
Indications for chromosome analysis in adolescence/adults
Balanced chromosome aberrations
Inversions (inv) - pericentric
Inversions (inv) - paracentric
Inversions - meiosis
-> small inversion -> curve formation -> no-crossing-over
-> big inversion -> loop formation to prevent mis-alignment -> chromatids with partial loss/gain, normal and inverted
-> always loop formation
crossing over -> chr. with 2 centromers -> loss of chromosome
crossing over -> chr. w/o centromere -> can’t be attached to spindle apparatus -> loss of chromosome
loss of chromosome -> monosomy = very severe (no back up)
Unbalanced chromosome aberrations
Translocations - robertsonian translocation
Translocations - reciprocal translocation
Translocations - insertional translocation
Robertosonian translocation - chromosomes likely to fuse / acrocentric chromosomes
Unbalanced chromosome aberrations - numerical
(a) Diandric = 2x male + 1x female
large placenta
cystic structure (partial mole)
fetus of normal size and small head
(b) Digynic = 2x female + 1x male
small placenta
fibrotci placenta
small fetus with disproportional large head
(c) paternal disomy
risk of malignancy for mother (due to invasive placenta)
no fetus
Aneuploidy - hyperdiploidy
Aneuploidy - hypodiploidy
Turner syndrome
= 45, X (only viable monosomy) ; X lost AFTER first division
short stature
infertile
no secondary sex characteristics
lymphedema at birth
if X lost BEFORE first division -> very severe / lethal
Unbalanced chromosome aberrations - structural
types of unbalanced structural chromosome aberrations
deletion (del)
duplication (dup)
terminal
inverted duplication
interstitial
tandem duplication
ring chromosome (break in p- & q-arm; loss of material of both (rest)) (r)
isochromosome (i)
Wolf-Hirschhorn-syndrome
= deletion in 4p —> degree of severity depends on size of deletion
common symptoms
prenatal dystrophy
facial: wide-spread eyes + low nasal bridge + low set ears
postnatal growth retardation
severe psychomotor retardation
malformation
brain -> epilepsy
eye -> esp. iris coloboma
renal
genital
Cri-du-chat syndrome
= deletion in 5p —> severity depends on size of deletion
babies cry like cats
general:
muscular hypotonia
head:
low set dysplastic ears
round face + small chin (young age)
broad nasal root
eyes: strabism (Schielen)
congenital heart defects
De-Grouchy-I-syndrome
De-Grouchy-II-syndrome
= deletion of 18p (short arm)
= deletion of 18q (long arm)
pre- and postnatal dystrophy
round face + small chin
heart defects
microcephaly
global retardation
higher risk of autoimmune disorders
cleft lip and palate
dysmorphisms
TCF4 gene -> severe epillepsy
Isochromosome (i)
Mosaicism
= existence of at least 2 genetically different cell lines, which are derived from one zygote
characteristics
percentage of the different cell lines varies between different tissues
no definite relationship between percentage of abnormal cells and clinical symptoms
percentage of abnormal cells can shift during life and often becomes less
Pallister-Killian-syndrome = mosaicism for tetrasomy 12p (47, …, +i(12)(p10) = isochromosome (derived of short arms from chr. 12))
can’t be found in blood cells -> need skin fibroblasts
severe intellectual diability
syndactyly
hair growth only on top of head, but not on the sides
pigmentary changes
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