11/4- Can You Hear Me Now

Question 1

_(how many)__ genes are involved in hearing loss?

Answer 1

Hundreds of genes are involved in hearing loss

Question 2

What are the 3 types of hearing loss?

Answer 2

Three types of hearing loss:

• Conductive
• Sensorineural
• Mixed

Question 3

When many genes can each cause the same phenotype, we call the phenotype _____

Answer 3

When many genes can each cause the same phenotype, we call the phenotype:

• Genetically heterogeneous
• Locus heterogeneity

Question 4

When many different mutations in a single gene can cause the same phenotype, we call the phenotype _____

Answer 4

When many different mutations in a single gene can cause the same phenotype, we call the phenotype allelic heterogeneity

Question 5

When mutations in 2+ genes contribute to a phenotype in and individual, the phentoype is ______

Answer 5

When mutations in 2+ genes contribute to a phenotype in and individual, the phentoype is polygenic/multigenic

Question 6

When both a gene(s) and the environment contribute to a phenotype in an individual, the phenotype is ___

Answer 6

When both a gene(s) and the environment contribute to a phenotype in an individual, the phenotype is multifactorial

Question 7

What is genetically heterogeneous/locus heterogeneity?

Answer 7

When many genes can each cause the same phenotype

Question 8

What is allelic heterogeneity?

Answer 8

When many different mutations in a single gene can cause the same phenotype

Question 9

What is a polygenic/multigenic phenotype?

Answer 9

When mutations in 2+ genes contribute to a phenotype in and individual

Question 10

What is a multifactorial phenotype?

Answer 10

When both a gene(s) and the environment contribute to a phenotype in an individual

Question 11

What are the 5 hearing loss syndromes we need to know? (list)

Answer 11

1. Branchio-Oto-Renal Syndrome
2. Jervell and Lange-Nielson syndrome
3. Pendred syndrome
4. Usher syndrome
5. Waardenburg syndrome

Question 12

In addition to hearing loss, what else is seen in Branchio-Oto-Renal syndrome?

Answer 12

• Ear pits
• Oozing pit in neck
• Single kidney

Question 13

In addition to hearing loss, what else is seen in Jewell and Lange-Nielson syndrome?

Answer 13

• Long QT
• FHx of sudden death

(- Parents are typically carriers of Romano-Ward?)

(- Recessive)

Question 14

In addition to hearing loss, what else is seen in Pendred syndrome?

Answer 14

• Goiter

Question 15

In addition to hearing loss, what else is seen in Usher syndrome?

Answer 15

• Retinitis pigmentosa (will lose vision)

Question 16

In addition to hearing loss, what else is seen in Waardenburg syndrome?

Answer 16

• Heterochromia (different colors of eyes, or differently-colored single piece of an eye)
• Early greying

*Think of this if you see hearing loss and crystalline blue eyes in dark-skinned child

Question 17

Non-syndromic hearing loss has what kind of genetic contribution (think of those vocab words)

Answer 17

• Genetically heteogeneous
• Locus heterogeneity

Question 18

What is the “big fish” gene locus responsible for non-syndromic autosomal recessive hearing loss?

Answer 18

13q

Question 19

The __________ mutation is the gene found in the 13q locus responsible for hearing loss

Answer 19

The GJB2, connexin 26 mutation is the gene found in the 13q locus responsible for hearing loss

• Autosomal recessive
• Non-syndromic

Question 20

There is a __% carrier rate for connexin 26 mutations

Answer 20

There is a 3% carrier rate for connexin 26 mutations

Question 21

What is the incidence of connexin 26 related hearing loss in the general population? (be able to do this kind of math on the test)

Answer 21

Carrier rate = 3/100

Chance of passing on from one parent = 1/2

So, (3/100)(3/100)(1/2)(1/2) for both parents = 9/40,000

Question 22

What is the incidence of connexin 26 related hearing loss if one parent is homozygous recessive (has this hearing loss)?

Answer 22

(3/100)(1/2) = 3/200

Question 23

What management should be done for all children with autosomal recessive non-syndromic hearing loss?

Answer 23

They should be screened for connexin 26!

(DON’T DO if it appears syndromic, with a bunch of other signs/symptoms)

Question 24

What should be used as a “net” for other hearing loss genes? What does this include?

Answer 24

Next Generation Sequencing (sequencing info on many genes at once)

• Panels: screen many genes
• Whole exome: sequence all exons
• Whole genome: sequence everything
• Any disease that has locus heterogeneity

DON’T DO SINGLE GENE SEQUENCING (takes money and time)

Question 25

Summary slide

Answer 25

• Know the main types of hearing loss
• What does genetically heterogeneous mean
• What are the 5 types of syndromic hearing loss
• What is the most common cause of non-syndromic hearing loss
• Do I know how to estimate incidence and calculate hearing loss risk for families
• Do I understand when I should consider using next generation sequencing