Molecular and Clinical Analysis Of Aneuploidies
By Mona Javaheri, Mahdieh Fallahi
QF PCR
Medical Genetics Laboratory of Dr. Zeinali
Molecular Analysis
Aneuploidies that are compatible with life
Down Syndrome/Trisomy 21
Patau Syndrome/Trisomy 13
Edwards Syndrome/ Trisomy 18
Turner Syndrome/ Monosomy X
Triple X Syndrome
Klinefelter syndrome
Jacob Syndrome
Triploidy
Molecular Analysis
First and Second trimester screening
Combined Test
Quad Screen
Integrated Test
Molecular Analysis
Amniotic Fluid/Chorionic Villus Sampling
DNA Extraction
Analysis of gene dosage of 13,18,21 and x/y chromosomes using QF PCR
Analysis of PCR products using Genetic Analyzer Software
QF PCR kit
Aneuquick /Aneufast Kit
Labelled Markers For 13,18,21,X/Y Chromosomes
FAM/HEX/NED/PET
Molecular Analysis
DOWN SYNDROME
Down syndrome is one of the most common chromosome abnormalities in
humans
About one per 1000 babies born each year
Problems
Physical growth delay
facial features
intellectual disability
patterns on the fingertips
DOWN SYNDROME
• Eye and ear problems
• Congenital heart disease
• Cancer
• Endocrine
• Gastrointestinal
• Fertility
Edwards syndrome
Edwards syndrome occurs in around one in 6,000 live births, and around 80% of those
affected are female
The incidence increases as the mother's age increases
20-30% die early in First month of live
Problems
Heart Problems
Feeding difficulties
Edwards syndrome
Arthrogryposis:
• Clubfoot or rocker bottom feet
• In males, undescended testicles , cleft lip/cleft palate
Signs during the pregnancy:
• The presence of choroid plexus cysts
• Excess amniotic fluid or polyhydramnios
• Small Placenta
• Decrease the fetus Movement
Patau syndrome
One per 10000 Live Birth
Intellectual disability
Microcephaly
Holoprosencephaly
Structural eye defects
Meningomyelocele (a spinal defect)
Musculoskeletal problems
Patau syndrome
Deformed feet known as rocker-bottom feet
Omphalocele (abdominal defect)
Overlapping of fingers over thumb
Cleft palate
Abnormal genitalia
Kidney defects/Heart Single umbilical artery
45% die early at the first month of live
Turner syndrome
Increased weight, obesity
Shortened metacarpal
Small fingernails
Webbed neck from cystic hygroma in infancy
Horseshoe kidney
Visual impairments
High waist-to-hip ratio
Attention deficit hyperactivity disorder
Turner syndrome
Absence of one complete or partial copy of the X chromosome in some or all the
cells.
X (monosomy) (45,X)
partial monosomy like a deletion of the short p arm of one X chromosome
(46,X,del(Xp))
the presence of an isochromosome with two q arms (46,X,i(Xq))
mosaic Forms
Ring chromosome
The presence of mosaicism is estimated to be relatively common in affected
individuals (67–90%)
Turner syndrome
The functional X chromosome mostly comes from the mother
Balanced translocation of the X chromosome in a parent, or where the
mother has 45,X mosaicism restricted to her germ cells
Jacob syndrome
Extra male (Y) chromosome, giving a total of 47 chromosomes instead of the more usual
46. 47,XYY karyotype
Occurs every 1 in 1,000 male births.
Increased growth velocity from early childhood
The increased gene dosage of three X/Y chromosome pseudoautosomal
region(PAR1) SHOX
Severe acne
Testosterone levels
The incidence of 47,XYY is not affected by advanced paternal or maternal age
Triploidy
Extremely rare chromosomal disorder
Have three of every chromosome
Fetuses with triploid syndrome are usually lost through
early miscarriage
Small and have multiple birth defects. Those who survive are
usually mosaic
Triple X Syndrome
Trisomy X occurs during cell division in early embryonic development
The vast majority of Triple X women are never diagnosed 46,XX/47,XXX mosaics
Having 2 Bar bodies
Mild mental retardation
Irregular Menstruation
Klinefelter syndrome
Also known as 47,XXY or XXY, is the set of symptoms that result from
two or more X chromosome in males
An older mother might increase the risk slightly
Klinefelter syndrome
Signs and symptoms
Physical
As baby/During puberty/By adulthood
XXY males are also more likely than other men to have certain health
problems that typically affect females
Decreased testicular hormone/endocrine function
infertility
Klinefelter syndrome
Cognitive and developmental
language learning or reading impairment
XXY males may sit up, crawl, and walk later than other infants
Struggle in school, both academically and with sports
Trisomy 16
This chromosome represents almost 3% of all DNA in cells
Full trisomy 16 is incompatible with life and most of the time it results
in miscarriage during the first trimester
It is the most common trisomy leading to miscarriage and the second
most common chromosomal cause of it, closely following X
chromosome monosomy
Trisomy 16
Mosaic trisomy 16
Compatible with life
The most common malformations were CSD, ASD, and hypospadias