Fig. 3

Challenging variants that are not detected by exome. A Pedigree of family F7974 with two sisters affected with band keratopathy. B Clinical images of individual (IV:6) highlighting keratopathy phenotype. C RT-qPCR experiment showing reduced SLC4A4 transcript levels compared to two independent controls. D Pedigree of family F4591 with three cousins affected with microcephalic NDD. E and F MRI imaging of individual (IV:8) showing mild brain atrophy and thin corpus callosum. G RT-qPCR results demonstrating reduced expression of SNAP91 in three patients compared to two independent controls. H Pedigree of family F5927 with four children affected with NDD. I and J Clinical images of individuals (II:3 and II:4) highlighting microcephaly and progressive spasticity. K RT-qPCR experiment showing consistently reduced LEMD2 expression levels in samples from four affected siblings compared to two independent controls. L and M Nuclear morphology of patient cells compared to two independent controls and representative images highlighting abnormal nuclear morphology using red arrows. Error bars denote standard deviation of at least 3 experiments. ****, ***, ** denote p-values < 0.0001, < 0.001, and < 0.01, respectively, using unpaired Student’s t-test