List of the mutations found in USH genes.

<p>List of the mutations found in USH genes.</p

Predicted effect of the p.Tyr39His and p.Asp1501Asn <i>CDH23</i> mutations.

<p>(A) On the left side, ribbon diagram of protocadherin-15 EC1-EC2 (pink) bound to cadherin-23 EC1-EC2 (blue). Ca²⁺ ions are depicted as green spheres. The Tyr39 residue of cadherin-23 is shown in yellow. On the right side, detailed cartoon of the cadherin23-protocadherin15 interaction interface. The Tyr39 residue engages in van der Waals interactions with Ile22 and Val114 of protocadherin-15, and the substitution of this residue by His (orange) is not predicted to change these interactions. (B) On the left side, ribbon diagram showing the backbone of cadherin-23 EC1-EC2 and the side chains of the amino-acid residues involved at the Ca²⁺-binding interface of the EC1-2 linker. On the right side, detailed cartoon of the corresponding Ca²⁺-binding site in the EC14-15 linker. The Asp1501 residue is shown in yellow. Lower panel: the substitution of this residue by Asn (orange) causes steric clashes or charge incompatibility in all three modeling rotamers, and is therefore predicted to impair Ca²⁺-binding.</p

Predicted effect of the p.Ala397del <i>USH1G</i> mutation.

<p>(A) On the left side, ribbon diagram showing the hydrophobic core of the SAM domain of USH1G/sans. The side chains of the hydrophobic residues Leu392, Phe395, Leu396, and Leu399 and of the polar residue His400 of the αA helix are represented in green and in blue, respectively. On the right side, the ribbon diagram shows the disruption of the hydrophobic core of the SAM domain by the His400 polar residue in the presence of the p.Ala397del mutation. (B) On the left side, ribbon diagram showing the overall structure of the Nter-PDZ1 domain of USH1C/harmonin (cyan) interacting with the SAM domain of USH1G/sans (orange). The αA helix of the SAM domain interacts with the surface groove of the harmonin PDZ1 domain. Note the major involvement of the SAM domain residues Thr394, Ala397, and His400 in this interaction. On the right side, the ribbon diagram shows the abnormal SAM-PDZ1 interaction interface in the presence of the p.Ala397del mutation: the Leu151 and Thr156 residues of the PDZ1 domain cannot interact with the missing Ala397 residue and the His400 residue of the SAM domain, respectively.</p

Schematic representation of myosin-VIIa (USH1B), harmonin (USH1C), cadherin-23 (USH1D), protocadherin-15 (USH1F), sans (USH1G), and usherin (USH2A).

<p>For each protein, the longest isoform is shown. The novel and the previously reported causal mutations in Algerian USH patients are indicated in red and in black, respectively. Abbreviations: <i>IQ</i>, isoleucine-glutamine motifs; <i>MyTH4</i>, myosin tail homology 4 domain; <i>FERM</i>, band 4.1-ezrin-radixin-moesin domain; <i>SH3</i>, src homology 3 domain; <i>Nter</i>, N-terminal domain; <i>PDZ</i>, PSD95-discs large-ZO1 domain; <i>CC</i>, coiled coil domain; <i>PST</i>, proline-serine-threonine-rich region; <i>EC</i>, extracellular cadherin domain; <i>TM</i>, transmembrane domain; <i>Ank</i>, ankyrin domain; <i>SAM</i>, sterile alpha motif domain; <i>LamG/TspN/PTX</i>, N-terminal thrombospondin/pentaxin/laminin G-like domain; <i>Lam Nter</i>, laminin N-terminal domain; <i>Lam EGF-like</i>, laminin-type EGF-like domain; <i>Lam G-like</i>, laminin G-like domain; <i>FNIII</i>, fibronectin type III domain.</p

DNA sequence electropherogram showing the boundaries of the large deletion identified in <i>PCDH15</i>.

<p>The PCR intronic primers used to define the boundaries of the deletion identified in the USH1F patient were PCDH15-intron9Forward (5'-GAAATCCCTTGACCCCTTGT-3') and PCDH15-intron14Reverse (5'-GCAAAGACTTGGAACCAACC-3'), leading to an amplicon of approximately 1.2 Kb.</p

Predicted pathogenicity of the six missense mutations found in Algerian USH patients.

<p>Predicted pathogenicity of the six missense mutations found in Algerian USH patients.</p

Retinal phenotypes of patients with mutations in Usher genes.

<p><b>A</b>, Composite color fundus photograph of the left eye of a four-year-old girl (DF103-III-2) showing diffuse narrowing of the retinal arteries and hyperpigmentation in a bone-spicule configuration in the midperipheral retina. <b>B</b>, B-scan OCT imaging of the same eye showing a mild foveal atrophy (central macular thickness = 160 micrometers). <b>C</b>, Color fundus photograph of the posterior pole of the right eye of a six-year-old boy (DF103-III-1) with early stage retinitis pigmentosa shows no obvious abnormalities which may explain the misdiagnosis of the disease in some cases. <b>D</b>, Color fundus photograph of the peripheral retina showing a “salt and pepper" appearance without the classical bone-spicule pigmentation. <b>E</b>, The fovea has a normal thickness on optical coherence tomography (180 micrometers).</p

Pedigrees of the four Tunisian patients analyzed by whole exome sequencing.

<p>Squares and circles denote males and females, respectively. Filled symbols indicate deaf individuals. Arrows indicate the individuals analyzed by WES.</p

Evolution of the number of variants during whole exome.

<p>Evolution of the number of variants during whole exome.</p

Pedigrees of the four Tunisian families analyzed using the whole exome sequencing strategy.

<p>Pedigrees of the four Tunisian families analyzed using the whole exome sequencing strategy.</p