Clinical Genetics 13.1 B +Down Syndrome13.2

Question 1

What is thr micro deletion in Williams Syndrome

Answer 1

7q11

Question 2

What is the micro deletion in digeorge syndome/velocardiofacial?

Answer 2

22q11

Question 3

What is the point mutation in Cystic fibrosis?

Answer 3

Missense: codon 117 ( CGC > CAC) (Arg>His)

Nonsense: codon 493 (CAG >TAG) (gln> stop codon)

Question 4

What is the cutoff limit of CAG repeats to produce Huntington disease?

Answer 4

> 37

Question 5

Genetic mutations in Tuberous Sclerosis

Answer 5

TSC1 9q : Hamartin protein (tumor suppressor)

TSC2 16p : Tuberin

Question 6

What is the gene mutation in Neurofibromatosis type 1

Answer 6

17q : neurofibromin (Tumor suppressor)

Question 7

Mutation of Achondroplasia

Answer 7

FGFR3 gene on Chr. 4 (gain of function mutation) Autos. Dom.

Question 8

Fibrillin 1 gene mutation is associated with…

Answer 8

Marfan Syndrome

Question 9

Cystic fibrosis mutation is on which chromosome?

And what is the commonest mutation? What is the diagnostic Test?

Answer 9

Chr. 7, CFTR gene
Commonest mutation: dF508
Sweat test >60

Question 10

What is the Mutation site in Fragile X syndrome

Answer 10

Xq28
Increased CGG repeats
... No. Of repeats
 normal:5-44
Premutation: 55-200
Mutation >200

Question 11

What is the most common cardiac condition affecting William syndrome?

Answer 11

Supravalvular aortic Stenosis

Question 12

Mode of inheritance of Tuberous Sclerosis

Answer 12

AD

Question 13

Mode of inheritance of Neurofibromatosis

Answer 13

AD

Question 14

Mode of inheritance of Achondroplasia

Answer 14

AD

Question 15

Mode of inheritance of Cystic Fibrosis

Answer 15

AR

Question 16

Genetic causes of Down syndrome

Answer 16

Nondisjunction
Unbalanced translocation(robertsonian) (14q; 21q)
Mosaicism

Question 17

What are the acrocentric chromosomes

Answer 17

13, 14, 15

21, 22

Question 18

Antenatal diagnosis of Down syndrome

Answer 18

Non invasive
• 1st trimester screen (11-14 weeks) maternal age risk +
ØThick nuchal translucency
Øserum human chorionic gonadotropin (β-hCG)
ØPregnancy associated plasma protein A (PAPP-A)
Detection rate 82-87%
• 2nd trimester screen (quad screen) maternal age risk +
(serum hCG, unconjugated estriol, α-fetoprotein (AFP), inhibin levels)
Detection rate 80%
• NIPT (Detection rate 99%) at 10-11 weeks of gestation
Invasive
Amniocentesis or CVS and chromosomal testing