Principles of Genetic Disease

Question 1

Autosomal dominant. Pigmentary disturbance, wide nasal bridge due to lateral displacement of the inner canthus of the eye and cochlear deafness.

Answer 1

Waardenburg syndrome

Question 2

50% expression not sufficient for normal function

Answer 2

Haploinsufficiency

Question 3

When defective protein is not only nonfunctional but it inhibits function of normal counterparts. Example is osteogenesis imperfecta

Answer 3

Dominant negative

Question 4

The level of protein product produced by a gene can produce different phenotypes at various levels, rather than one phenotype in the presence of the protein and one in the absence or at a threshold level. The same gene can produce different disease manifestations depends upon the type of mutation present

Answer 4

Dosage sensitivity

Question 5

Demyeliniation is the hallmark pathology. Neuropathy involves loss of PNS motor and sensory neurons that are connected to muscles and sensory receptors.

Answer 5

Charco-Marie-Tooth Disease

Question 6

Caused by duplications in PMP22. Autosomal dominant.

Answer 6

Charcot-Marie-Tooth Disease Type 1A

Question 7

Caused by deletions in PMP22. Autosomal dominant. Unlike the affected nerves in Charcot-Marie-Tooth, these have focal regions with “tomaculous” changes or sausage shaped figures due to the irregular thickening of the myelin sheath. Considered less severe than CMT

Answer 7

Hereditary Neuropathy with Inability to Pressure Palsies (HNPP)

Question 8

Autosomal recessive. Clinically similar to Charcot-Marie-Tooth but is very severe and occurs in infancy

Answer 8

Dejerine-Sottas Syndrome (DSS)

Question 9

A mutation that occurs in every cell in an individual and that was therefore inherited from a parent.

Answer 9

germline mutation

Question 10

a mutation occurring only in a subset of somatic cells.

Answer 10

somatic mutation

Question 11

The occurrence of more than one disease causing allele at a locus

Answer 11

allelic heterogeneity

Question 12

The association of more than one locus with a specific clinical phenotype

Answer 12

locus heterogeneity

Question 13

variability in relation to presentation or treatment of a disease.

Answer 13

clinical heterogeneity

Question 14

Genes that affect the occurrence or severity of a phenotype associated with mutations in a non-allelic gene. These can be factors in clinical heterogeneity.

Answer 14

modifier genes

Question 15

alleles of genes containing epigenetic marks. these can include forms of histone modification or DNA methylation

Answer 15

epiallele

Question 16

Caused by maternal inheritance of deletions. Unusual facial appearance, short stature, severe mental retardation, spasticity, seizures.

Answer 16

Angelman Syndrome

Question 17

Caused by paternal inheritance of deletions. Obesity related to eating disorder, small hands/feet, short stature, hypogonadism, mental retardation.

Answer 17

Prader-willi syndrome

Question 18

inactivation of a gene

Answer 18

gene silencing

Question 19

determination of the expression of a gene by its parental origin.

Answer 19

imprinting