Genetics

Question 1

What type of genetic disorder if Neurofibromatosis

Answer 1

Autosomal Dominant with 100% penetrance (NFM1 gene)

• Cafe au lait macules
• Neurofibromas
• Benign CNS tumors/occular
• Macules in the iris (leash nodules)

Question 2

What type of genetic disorder if Marfan’s Syndrome

Answer 2

Autosomal Dominant with incomplete penetrance with variable expressivity (FBN 1 gene)

• Posterior dislocate of the lens
• Pectus excavatum

Question 3

Duchenne Muscular Dystrophy

Answer 3

X-Linked Recessive

Question 4

Haemophilia A

Answer 4

X-Linked Recessive

Question 5

Fabry Disease

Answer 5

X-Linked Recessive

Question 6

Haemachromatosis

Answer 6

Autosomal Recessive

Question 7

Turner Syndrome

Answer 7

45X (Monosomy)

• Short stature
• Ovarian dysgenesis
• Lack of secondary sex characteristics
• Infetility
• Congential problems with heart and kidney’s

Question 8

Klinefelter Syndrome

Answer 8

47XXY (Trisomy)

• Secondary sex characteristics
• Testicular atrophy
• Infertility

Question 9

Prader-Willi syndrome

Answer 9

Deletion of paternal Chromosome 15 or paternal disomy.

Loss of expression of SNERPIN region of chromosome 15
Materanlly imprinted (therefore rely on paternal copy) 

Question 10

Angelman syndrome

Answer 10

Deletion of maternal Chromosome 15 or paternal disomy.

Intellectual impairment
Wide mouth with thin upper lip
Ataxia with wide based gait

Question 11

Characteristics of trinucleotide repeats

Answer 11

1) Intergenerational instability
2) Anticipation (phenotype can get worse over generations)
3) Premutation
4) Sometime genotype-phenotype correlation

Question 12

Myotonic dystrophy

Answer 12

Due to trinucleotide repeat pattern 
Thresholds: >50 = disease <37 = no disease 
- Muscle weakness
- Myotonia
- Infertility
- Male pattern baldness

Question 13

Fragile X Syndrome

Answer 13

Males > Females
Trinucleotide repeat (CGG repeat)
50-200 = permutation, >200 = disease
- Intellectual disability

Question 14

Huntington disease

Answer 14

Trinucleotide repeat (CAG repeat)
Anticipation
Threshold
< 29 = Normal, children unlikely to be affected
>29 = unstable, children may develop
>36 = Some will develop disease, children (especially of men )
> 40 = All will develop HD

• Chorea
• Cognitive impairment
• Psychiatric symptoms

Question 15

Neurofibramatosis chromosomal locations

Answer 15

NF 1 = 17

NF 2 = 22

Question 16

Tuberous Sclerosis

Answer 16

TS 1 = 9

Ts 2 = 16

Question 17

Gold standard diagnosis of Muscular Dystrophy

Answer 17

Genetic testing for an expanded CTG repeat in the DMPK gene

Question 18

On which chromosome is the CFTR gene present?

Answer 18

Chromosome 7

Question 19

A man presents with Burkitt lymphoma and is found to have the 8;14 translocation in the tumor. This translocation activates an oncogene with which of the following functions?

Answer 19

MYC oncogene which functions as a pleiotropic transcriptional regulator of cell proliferation, differentiation, and apoptosis

Question 20

On which chromosome is the HFE gene present?

Answer 20

Chromosome 6

Question 21

On which chromosome is the Von Williebrands factor gene present?

Answer 21

Chromosome 12

Question 22

Inheritance of homocystinuria

Answer 22

Rare autosomal recessive disorder.

Characterized by severe elevations in plasma and urine homocysteine concentrations

Question 23

Genotype of homocystinuria

Answer 23

Loss of function mutation in the CBS gene resulting in a deficiency of cystathionine B synthesise. This affects the metabolism of the amino acid methionine leading to an elevation of homocystinuria.

Question 24

Inheritance of Fragile X

Answer 24

X-linked disorder and the most common inherited cause of intellectual disability

Question 25

Genetics of Fragile X

Answer 25

Loss-of-function mutation in the fragile X mental retardation 1 (FMR1) gene –> to an expansion of the CGG triplet repeat –> leading to reduced levels of fragile X mental retardation protein (FMRP).

Question 26

What is the typical inheritance pattern of Alport syndrome?

Answer 26

X-linked

Question 27

Which of the following is the most common single gene found in maturity onset diabetes of the young (MODY)?

Answer 27

Hepatic nuclear factor 1 alpha (50%)
Glucokinase (20%)

Mutated GCK = MODY 2 = high fasting glucose but do no go on to develop diabetes

Mutated HNF1alpha/HFN4alpha respond particularly well to oral sulphonureas

Mutated HFN1Beta also causes renal cysts and renal failure

Question 28

Formula for incidence in rare AR using the carrier frequency

Answer 28

Carrier Frequency = 2 x square root of incidence

Question 29

What is Karyotype useful in identifying

Answer 29

Trisomy, Aneuploidy