000203988 001__ 203988
000203988 005__ 20181203023716.0
000203988 0247_ $$2doi$$a10.1136/bjophthalmol-2014-305231
000203988 022__ $$a0007-1161
000203988 02470 $$2ISI$$a000345284300022
000203988 037__ $$aARTICLE
000203988 245__ $$aNovel ADAM9 homozygous mutation in a consanguineous Egyptian family with severe cone-rod dystrophy and cataract
000203988 260__ $$bBmj Publishing Group$$c2014$$aLondon
000203988 269__ $$a2014
000203988 300__ $$a6
000203988 336__ $$aJournal Articles
000203988 520__ $$aObjective To genetically and phenotypically describe a new ADAM9 homozygous mutation in a consanguineous family from Egypt with autosomal recessive cone-rod dystrophy (arCRD), anterior polar and posterior subcapsular cataract. Design, setting and participants The parents and their six children were included. They underwent a complete ophthalmic examination with fundus photography and optical coherence tomography (OCT). Intervention DNA was extracted from peripheral blood from all family members. Screening for mutations in genes known to be implicated in retinal disorders was done with the IROme, an in-solution enrichment array, followed by high-throughput sequencing. Validation of the results was done by bidirectional Sanger sequencing of ADAM9 exon 14, including exon-intron junctions. Screening of normal controls was done by denaturing high-performance liquid chromatography. Results arCRD was diagnosed in the mother and two of her children. Bilateral anterior polar and posterior subcapsular cataract was observed in the mother and bilateral dot cataract was diagnosed in three of the four children not affected with arCRD, one of whom also had glaucoma. The characteristics of the arCRD were childhood-onset visual impairment, reorganisation of the retinal pigment epithelium with mid-periphery greyish-white discolouration, attenuated retinal vasculatur and optic disc pallor. A coloboma-like macular lesion was observed in one of the arCRD-affected children. IROme analysis identified a c. 1396-2A>G homozygous mutation in the splice acceptor site of intron 13 of ADAM9. This mutation was homozygous in the two children affected by arCRD and in their affected mother. This mutation was heterozygous in the unaffected father and the four unaffected children. Conclusions and relevance We identified a novel autosomal recessive ADAM9 mutation causing arCRD in a consanguineous Egyptian family. The percentage of arCRD cases caused by mutation in ADAM9 remains to be determined. Few families are reported in the literature to date; hence extensive clinical descriptions of families with ADAM9 mutations are of significant importance.
000203988 700__ $$uZagazig Univ, Dept Ophthalmol, Zagazig, Egypt$$aEl-Haig, Wael M.
000203988 700__ $$uInst Res Ophthalmol, CH-1950 Sion, Switzerland$$aJakobsson, Cecilia
000203988 700__ $$uInst Res Ophthalmol, CH-1950 Sion, Switzerland$$aFavez, Tatiana
000203988 700__ $$uInst Res Ophthalmol, CH-1950 Sion, Switzerland$$aSchorderet, Daniel F.
000203988 700__ $$uInst Res Ophthalmol, CH-1950 Sion, Switzerland$$aAbouzeid, Hana
000203988 773__ $$j98$$tBritish Journal Of Ophthalmology$$k12$$q1718-1723
000203988 909C0 $$xU10445$$0252372$$pSV
000203988 909CO $$pSV$$particle$$ooai:infoscience.tind.io:203988
000203988 937__ $$aEPFL-ARTICLE-203988
000203988 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000203988 980__ $$aARTICLE