Whole Exome Analysis Identifies Frequent <i>CNGA1</i> Mutations in Japanese Population with Autosomal Recessive Retinitis Pigmentosa

<div><p>Objective</p><p>The purpose of this study was to investigate frequent disease-causing gene mutations in autosomal recessive retinitis pigmentosa (arRP) in the Japanese population.</p><p>Methods</p><p>In total, 99 Japanese patients with non-syndromic and unrelated arRP or sporadic RP (spRP) were recruited in this study and ophthalmic examinations were conducted for the diagnosis of RP. Among these patients, whole exome sequencing analysis of 30 RP patients and direct sequencing screening of all <i>CNGA1</i> exons of the other 69 RP patients were performed.</p><p>Results</p><p>Whole exome sequencing of 30 arRP/spRP patients identified disease-causing gene mutations of <i>CNGA1</i> (four patients), <i>EYS</i> (three patients) and <i>SAG</i> (one patient) in eight patients and potential disease-causing gene variants of <i>USH2A</i> (two patients), <i>EYS</i> (one patient), <i>TULP1</i> (one patient) and <i>C2orf71</i> (one patient) in five patients. Screening of an additional 69 arRP/spRP patients for the <i>CNGA1</i> gene mutation revealed one patient with a homozygous mutation.</p><p>Conclusions</p><p>This is the first identification of <i>CNGA1</i> mutations in arRP Japanese patients. The frequency of <i>CNGA1</i> gene mutation was 5.1% (5/99 patients). <i>CNGA1</i> mutations are one of the most frequent arRP-causing mutations in Japanese patients.</p></div

Sequence data of all six identified <i>CNGA1</i> mutations in this study.

<p>A-1 to F-1 show the normal sequence data for the <i>CNGA1</i> gene. A-2 to F-2 show the sequence data for heterozygous <i>CNGA1</i> mutations (c.191delG, c.265delC, c.G860A, c.G1271A, c.1429delG and c.G2042C, respectively). A-3 and B-3 show the sequence data for homozygous <i>CNGA1</i> mutations (c.191delG and c.265delC).</p

Pedigrees identified with arRP-causing mutations or potential arRP-causing variants.

<p>The solid squares (male) and circles (female) represent affected patients. The proband of each family is indicated by a black arrow. Unaffected family members are represented by white icons. The slash symbol indicates deceased individuals. The doubled line indicates consanguineous marriage. The generation number is shown on the left.</p

Ophthalmic findings in five patients with retinitis pigmentosa with compound heterozygous or homozygous <i>CNGA1</i> mutations.

<p>BCVA = decimal corrective visual acuity; ERG = electroretinography; M = male; F = female.</p><p>Ophthalmic findings in five patients with retinitis pigmentosa with compound heterozygous or homozygous <i>CNGA1</i> mutations.</p