11/4- Can You Hear Me Now Flashcards
_(how many)__ genes are involved in hearing loss?
Hundreds of genes are involved in hearing loss
What are the 3 types of hearing loss?
Three types of hearing loss:
- Conductive
- Sensorineural
- Mixed
When many genes can each cause the same phenotype, we call the phenotype _____
When many genes can each cause the same phenotype, we call the phenotype:
- Genetically heterogeneous
- Locus heterogeneity
When many different mutations in a single gene can cause the same phenotype, we call the phenotype _____
When many different mutations in a single gene can cause the same phenotype, we call the phenotype allelic heterogeneity
When mutations in 2+ genes contribute to a phenotype in and individual, the phentoype is ______
When mutations in 2+ genes contribute to a phenotype in and individual, the phentoype is polygenic/multigenic
When both a gene(s) and the environment contribute to a phenotype in an individual, the phenotype is ___
When both a gene(s) and the environment contribute to a phenotype in an individual, the phenotype is multifactorial
What is genetically heterogeneous/locus heterogeneity?
When many genes can each cause the same phenotype
What is allelic heterogeneity?
When many different mutations in a single gene can cause the same phenotype
What is a polygenic/multigenic phenotype?
When mutations in 2+ genes contribute to a phenotype in and individual
What is a multifactorial phenotype?
When both a gene(s) and the environment contribute to a phenotype in an individual
What are the 5 hearing loss syndromes we need to know? (list)
- Branchio-Oto-Renal Syndrome
- Jervell and Lange-Nielson syndrome
- Pendred syndrome
- Usher syndrome
- Waardenburg syndrome
In addition to hearing loss, what else is seen in Branchio-Oto-Renal syndrome?
- Ear pits
- Oozing pit in neck
- Single kidney
In addition to hearing loss, what else is seen in Jewell and Lange-Nielson syndrome?
- Long QT
- FHx of sudden death
(- Parents are typically carriers of Romano-Ward?)
(- Recessive)
In addition to hearing loss, what else is seen in Pendred syndrome?
- Goiter
In addition to hearing loss, what else is seen in Usher syndrome?
- Retinitis pigmentosa (will lose vision)
In addition to hearing loss, what else is seen in Waardenburg syndrome?
- 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
Non-syndromic hearing loss has what kind of genetic contribution (think of those vocab words)
- Genetically heteogeneous
- Locus heterogeneity
What is the “big fish” gene locus responsible for non-syndromic autosomal recessive hearing loss?
13q
The __________ mutation is the gene found in the 13q locus responsible for hearing loss
The GJB2, connexin 26 mutation is the gene found in the 13q locus responsible for hearing loss
- Autosomal recessive
- Non-syndromic
There is a __% carrier rate for connexin 26 mutations
There is a 3% carrier rate for connexin 26 mutations
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)
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
What is the incidence of connexin 26 related hearing loss if one parent is homozygous recessive (has this hearing loss)?
(3/100)(1/2) = 3/200
What management should be done for all children with autosomal recessive non-syndromic hearing loss?
They should be screened for connexin 26!
(DON’T DO if it appears syndromic, with a bunch of other signs/symptoms)
What should be used as a “net” for other hearing loss genes? What does this include?
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)
Summary slide
- 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
