22. Genetic disorders in children

Question 1

Base:

Answer 1

A unit of DNA. Human genome contains 3 billion base pairs.

Question 2

Gene:

Answer 2

A segment of DNA that codes for a protein.

Question 3

Chromosome:

Answer 3

A structure located in the nucleus all living cells, comprised of DNA bound around proteins called histones.

Question 4

Exome:

Answer 4

The coding portion of the genes. Constitutes 1-2 % of the genome.

Question 5

Genome:

Answer 5

All an individual’s genetic material including ≅20 000 genes and the genetic

Question 6

Tests for genetic disorders:

Answer 6

Karyotype
FISH – fluorescent in-situ hybridisation
QF-PCR – qualitative fluorescent polymerase chain reaction
Microarray

Question 7

What is FISH?

Answer 7

Fluorescent in-situ hybridisation, targeted method using probes to specific gene regions

Question 8

What is QF-PCR?

Answer 8

Qualitative fluorescent polymerase chain reaction.

• Amplifies specific regions of DNA
• Rapid, specific and accurate
• Only used for common aneuploidies

Question 9

What is microarray?

Answer 9

CGH – comparative genomic hybridisation

• Looks at amount of genetic material present
• More sensitive – picks up alterations at single level (3x more abnormalities than karyotype)

Question 10

What are the limitations of microarray?

Answer 10

Doesn’t detect balanced translocations, incidental finding, normal variants, or variants of uncertain significance

Question 11

Single gene disorders:

Answer 11

Mutations in single genes (Autosomal dominant, Autosomal recessive, X-linked recessive, X-linked dominant)

Question 12

Chromosome abnormalities examples:

Answer 12

Down syndrome (Trisomy 21)
Patau syndrome (Trisomy 13)
Edwards syndrome (Trisomy 18)
Turner syndrome (45 X0)
Kleinfelder’s Syndrome (47 XXY)

Question 13

Down syndrome:

Answer 13

Characteristic facial appearance (+ hypotonia, single palmar crease, wide sandal gap)

Question 14

What are the conditions associated with Down syndrome?

Answer 14

• ASD (congenital heart disease)
• Duodenal atresia
• Hirschsprung disease
• Hypothyroidism, Coeliac disease
• Visual and hearing impairment
• Increased risk of leukaemia

Question 15

Patau syndrome:

Answer 15

Small eyes, polydactyly, structural brain defects, cleft lip and palate, cardiac/renal problems

Question 16

Edwards syndrome:

Answer 16

Low birth weight, small chin, fixed overlapping fingers, ‘rocker- bottom’ feet, cardiac/renal problems

Question 17

Turner syndrome:

Answer 17

Short stature, infertility, widely spaced nipples, coarctation of aorta, neck webbing

Question 18

Kleinfelder’s syndrome:

Answer 18

Tall stature, infertility, educational/psychological problems