Table 1.
GREB1L variants associated with HI
| Family type | cDNA change* | amino acid change | Mode of inheritance | CADD score (v1.6) |
TopMed | gnomAD v3.1.2 | Hearing loss | Inner ear imaging phenotype | Country | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| Isolated |
c.347 C > T (rs1333304296) |
p.(Thr116Ile) | AD** | 27.2 | Absent | Absent | Profound bilateral SNHI | Bilateral cochlear aplasia, bilateral dysplastic vestibule and semicircular canals; bilateral cochlear nerve aplasia | Egypt | [14] |
| Familial | c.848 A > G | p.(Asn283Ser) | AD | 16.2 | Absent | Absent | Profound bilateral SNHI | NA | Pakistan | [14] |
| Isolated |
c.982 C > T (rs1555648043) |
p.(Arg328*) | de novo/ AD** | 36.0 | Absent | Absent | Profound bilateral SNHI |
Case 1: Bilateral cochlear aplasia, bilateral dysplastic vestibule and semicircular canals; bilateral cochlear nerve aplasia. Case 2: Cochlear hypoplasia type 1 (right): Cochlear aplasia with dilated vestibule (left) |
US, Korea | [11] [15] |
| Isolated | c.1079T > A | p.(Leu360*) | AD** | 36.0 | Absent | Absent | Profound bilateral HI | Cochlear aplasia with dilated vestibule (right): bilateral common cavity and Cochlear aplasia with dilated vestibule (left) | Korea | [15] |
| Isolated | c.3041G > A | p.(Gly1014Glu) | AD or de novo | 26.5 | Absent | Absent | Profound bilateral SNHI | NA | Ghana | This study |
| Isolated | c.4368G > T | p.(Glu1410fs) | de novo | 36.0 | Absent | Absent | Profound bilateral SNHI | Unilateral cochlear aplasia, unilateral incomplete partition type I, bilateral dysplastic vestibule and semicircular canals; bilateral cochlear nerve aplasia | US | [11] |
| Isolated | c.5618T > C | p.(Leu1873Pro) | AD** | 28.9 | Absent | Absent | Profound bilateral HI | Bilateral common cavity | Korea | [15] |
AD Autosomal dominantly inherited; NA Not available
*Based on NM_001142966.2. **Reduced penetrance seen in family.