Background
Methods
Clinical examination and family recruitment
Whole exome sequencing
In silico analysis of whole exome data
Sanger sequencing validation and segregation analysis
3D modeling
Results
Family history
Hearing loss | V-2 | V-3 | V-4 | V-5 |
---|---|---|---|---|
Approximate age of onset | Before 1 year old | Before 1 year old | Before 1 year old | Congenital |
Age at auditory examination | 1.6 years | ̴ 2 years | 7 months | 10 days |
Current age | 15 years | 4.4 years | 8 years | 2 years |
Type | Mixed | Sensorineural | Sensorineural | Sensorineural |
Laterality | Bilateral/symmetric | Bilateral/symmetric | Bilateral/symmetric | Bilateral/symmetric |
Suspected intrafamilial variability | No | No | No | Yes |
Degree | Profound | Profound | Profound | Severe |
Non-syndromic | Yes | Yes | Yes | Yes |
Identification and characterization of the c.323G>A variant
Family | |||
---|---|---|---|
Prediction of Variation | E30 | DEM4154 | PKDF1400 |
hg19 position, Chr.19 | 10,335,259 | 10,335,259 | 10,335,163 |
cDNA change | c.323G>A | c.323G>C | c.419A>G |
Amino acid change | p.Arg108Gln | p.Arg108Pro | p.Tyr140Cys |
ExAC | 0 | 0 | 0 |
gnomAD | 0 | 0 | 0 |
CADD | 34 | 21.7 | 22.9 |
MutationTaster | Disease causing | Disease causing | Disease causing |
SIFT | Deleterious | Deleterious | Tolerated |
PolyPhen-2 | Probably damaging | Probably damaging | Probably damaging |
ClinVar | No entry | Pathogenic | Pathogenic |
DVD | No entry | No entry | No entry |
HGMD | No entry | Hearing impairment, autosomal recessive | Hearing impairment, autosomal recessive |