SIX1 variants identified in subjects with CRS
| Family | 1 | 2 | 3 | 4 | 5 | 6 | 7 | |
| ID | 7081 | 163567 | F8566-1 (twin 1) | F8552-1 (twin 2) | L112-1 | 5692 | 1140 | 4531 |
| SIX1 variant | c.328C>T (p.R110W) | c.452C>T (p.P151L) | c.31C>T (p.Q11*) | c.31C>T (p.Q11*) | c.64C>T (p.Q22*) | c.373G>T (p.E125*) | c.40G>C (p.V14L) | c.513G>A (p.W171*) |
| Variant type (CADD score)* | Missense (33) | Missense (32) | Nonsense (38) | Nonsense (38) | Nonsense (37) | Nonsense (38) | Missense (24.4) | Nonsense (39) |
| Previously reported? | Recurrent in BOS/BOR | Novel† | Novel† | Novel† | Novel† | Novel† | Novel† | Novel† |
| Inheritance | De novo | Inherited (paternal) | Inherited (maternal) | Inherited (maternal) | Inherited (maternal) | Inherited (maternal) | De novo | Inherited (paternal) |
| Sutures affected | ||||||||
| Coronal (L, R) | +, + | |||||||
| Sagittal | + | + | + | + | + | + | + | + |
| Metopic | ||||||||
| Lambdoid (L, R) | +, + | +, + | +, + | +, + | ||||
| Syndromic features | Speech/language delay, ear pits/tags, unilateral neck sinus, sensorineural hearing loss. | No (borderline short stature, mild anteverted nares). | Branchial fistula. | Branchial fistula, restricted growth, posterior urethral valves. | Mild conductive hearing loss, unilateral branchial cyst/fistula. | No. | No (preauricular pits only). | No (occult bilateral branchial cysts). |
| Family history | Not applicable. | Not documented. | Branchial cysts, preauricular pit (maternal branch). | Hearing loss (maternal branch). | No. | Not applicable. | Moderate hearing loss (paternal branch). | |
*Combined Annotation Dependent Depletion score (CADD GRCh38-V.1.6).
†None of the novel variants is listed in gnomAD V.2.1.1 (minimum coverage ~245 000 alleles).15
BOR, branchio-oto-renal; BOS, branchio-otic syndrome; CRS, craniosynostosis; ID, identifier; L, left; R, right.