DiGeorge Syndrome

22q(del)
Individuals with the DiGeorge syndrome often
have cardiac defects, immune system
deficiencies and can be moderately retarded.
• The cause of the DiGeorge syndrome is a defect
in chromosome 22, where one of the bands in
the long arm has been deleted.
• The deletion can be suspected by looking at the
karyotype and can be confirmed by FISH.
 karyotype
• This image shows the karytype
of an individual with the
DiGeorge syndrome. By
looking carefully at the pair of
22's, you can see that there is a
light band missing in the
chromosome to the right. It
might be easier to see the defect
in the composite karyotype of
chromosome 22 from the same
individual.
 Fragile X Syndrome
• A condition characterized genotypically by
mutation of the distal end of the long arm of the X
chromosome (at gene loci FRAXA or FRAXE) and
phenotypically by cognitive impairment,
hyperactivity, SEIZURES, language delay, and
enlargement of the ears, head, and testes. MENTAL
RETARDATION occurs in nearly all males and
roughly 50% of females with the full mutation of
FRAXA.
enlargement of the ears, head, and
testes. MENTAL RETARDATION
occurs in nearly all males and roughly
50% of females
 Unusual Inheritance Patterens Due
to Genomic Imprinting
Genomic imprinting: the differential
expression of alleles depending on the
parent of origin.

Two microdeletion syndromes, Prader-Willi

syndrome and Angelman syndrome, are of particular
importance because they illustrate the newly
recognized phenomenon of genomic imprinting .
Each disorder has a distinct phenotype. PWS, a
neurobehavioral disorder affecting 1 in 10,000
newborns, has dysmorphic features that vary
throughout childhood, adolescence and adulthood.
These include hypotonia and poor sucking reflex,
hyperphagia leading to obesity, short stature and
extremities, and moderate mental retardation.
In contrast, AS features include hyperactivity,
laughter outbursts, clumsy, jerky movements, large
facial features, and severe mental retardation.
Both result from either a maternal or paternal
deletion on chromosome 15 or from uniparental
disomy, inheritence of both chromosomes of a pair
from one parent. The expression of these syndromes
is determined by parental origin of genes on
chromosome 15. 70% of all patients have the
deletion(15q11-q13). Only paternal deletions occur
in PWS and only maternal deletions in AS.

Uniparental disomy occurs when both

chromosomes of a pair are inherited from one
parent. In PWS two copies of chromosome 15 are
inherited from the mother, whereas, in AS two
copies are inherited from the father.
These observations suggest that certain autosomal
genes might be differentially expressed depending on
whether they were inherited from the father or from
the mother. Maternal and paternal genetic
contributions of autosomal genes are not necessarily
equivalent, and the genetic contributions from both
parents are necessary for normal development.
Changes in chromosome structure can take
various forms:
• Translocations e.g. balanced reciprocal translocation
46,XY,t(5;10)(p13;q25)
• Deletions e.g. Short arm deletion of 5, cri du chat
syndrome 46,XY,del(5)(p25)
• Ring chromosomes e.g. 46,XY,r(3)(p26q29)
• Duplications e.g. partial duplication 46XX,dup(2)
(p13p22)
• Inversions e.g. pericentric inversion 46,XY,inv (11)
(p15q14)
• Isochromosomes e.g. 46,X,I(Xq)
• Centric fragments e.g. centric fusion translocation
45,XX,t(13;14)(p11;q11)
 chromosomal disorder

 autosomal abnormalities Down syndrome

Numerial abnormalities trisomy 13

trisomy 18
Cri du chat syndrome
Structural abnormalities DiGeorge syndrome
Sex chromosome abnormalities
FRAX
Structural abnormalities
PWS,AS(imprinting)
Turner syndrome
Numerial abnormalities Klinefelter Syndrome
gonadal dysgenesis
Diagnosis ---karyotype analysis FISH

Sample:
blood cell, Individual after birth
amniotic fluid,
chorionic villus Fetus (Prenatal detection )

Treatment---No way
 Methods of making karyotype
1. Peripheral blood lymphocytes are separated off from
venous blood and added to nutrient medium which
stimulates T lymphocytes to divide.
2. The cells are cultured at 37oC for about 3 days and then
colchicine added to arrest cell division during
metaphase.
3. Hypotonic saline is then added which causes the cells
to swell and release the chromosomes which are then
fixed, mounted on a slide and stained for analysis.
4. Several different staining methods are used to enable
identification of individual chromosomes e.g.
5. G (Giemsa), Q (Quinacrine), R (Reverse) and C
(Centomeric heterochromatin) banding.
Fluorescence In Situ Hybridization (FISH)
Probes can be hybridized to the DNA contained
within chromosomes immobilized on microscope
slides. Athis technique is called in situ
hybrizization because the DNA in metaphase
chromosomes fixed on slides is denatured in
place to expose the two strands of DNA, thus
allowing a labeled probe to hybridize to the
chromosomal DNA. The most common method of
labeling probes for in situ hybridization to
chromosomes is with a flurescent dye.
Multicolor (24-color) FISH (mFISH): Metaphase chromosomes
from normal human fibroblasts after multicolor FISH
(mFISH). a) True or merged color profile from different
fluorochromes used. b) Computer generated pseudocolor image
of the same metaphase spread. Note each chromosome is
painted in a different color.