Figure 1.

Family 1 with autosomal recessive non-syndromic deafness and a non-manifesting homozygous AHI1 nonsense variant. (A) Pedigree (grey symbols: deaf individuals). Whole-exome sequencing of a sample from the index patient, II:3, did not identify a mutation either in any known deafness gene or in any strong candidate gene in any of the mapped HBD regions shared by II:3, II:5 and II:6. Four siblings were homozygous for the AHI1 nonsense variant p.Arg1066* (in purple = considered non-pathogenic). For clarity, the one-letter code (R1066*) was applied for variant designation. (B) Electropherograms depicting wild type (left), homozygosity (middle) and heterozygosity (right) for p.Arg1066*. (C–F) Cranial MRI of individuals II:4 (at the age of 34 years) and II:5 (at the age of 32 years) in comparison to MRI of two children with JBTS. (C1–F1) Axial sections at the level of the mesencephalon/superior cerebellar peduncles (scp): normal dimensions and orientation of the scp in C1 and D1, ‘molar tooth sign’ with thickened and elongated scp in E1 and F1 (red arrows). (C2–F2) Coronal sections, showing normal appearance of intervening vermis between the cerebellar hemispheres in C2 and D2, but ‘vermal cleft’ due to partial absence of the vermis in E2 and F2 (yellow arrows). (C3–F3) Mid-sagittal views illustrate normal brain stem morphology and normal tent-like triangular shape of the fourth ventricle in C3 and D3; the ‘tip’ of the fourth ventricle roof (fastigium) is at the level of mid-pons. In E3 and F3, the shape of the fourth ventricle is distorted, with rostral displacement of the fastigium, now at the level of mesencephalic-pontine boundary (blue arrowheads point to fastigium).