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Subjects were clinically diagnosed with suspected Kabuki syndrome. <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> revealed a homozygous nonsense mutation (c.5492dup, p.Asn1831Lysfs*8) in <jats:italic><jats:styled-content style=\"fixed-case\">VPS<\/jats:styled-content>13B<\/jats:italic> that is known to cause Cohen syndrome. The index case of family <jats:styled-content style=\"fixed-case\">MOL<\/jats:styled-content>1514 presented with both <jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content> and liver dysfunction, suspected initially to be related. <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> identified a homozygous frameshift mutation (c.1787_1788del, p.His596Argfs*47) in <jats:italic><jats:styled-content style=\"fixed-case\">AGBL<\/jats:styled-content>5,<\/jats:italic> associated with nonsyndromic <jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content>. The <jats:styled-content style=\"fixed-case\">MOL<\/jats:styled-content>1592 family included three affected subjects with crystalline retinopathy, skin ichthyosis, short stature and congenital adrenal hypoplasia, and were found to harbour a homozygous nonsense mutation (c.682C&gt;T, p.Arg228Cys) in <jats:italic><jats:styled-content style=\"fixed-case\">ALDH<\/jats:styled-content>3A2<\/jats:italic>, reported to cause Sj\u00f6gren\u2010Larsson syndrome (<jats:styled-content style=\"fixed-case\">SLS<\/jats:styled-content>). In the fourth family, <jats:styled-content style=\"fixed-case\">SJ<\/jats:styled-content>002, two siblings presented with hypotony, psychomotor delay, dysmorphic facial features, pathologic myopia, progressive external ophthalmoplegia and diffuse retinal atrophy. Probands were suspected to have atypical Kearns\u2010Sayre syndrome, but were diagnosed with combined oxidative phosphorylation deficiency\u201020 due to a novel suspected missense variant (c.1691C&gt;T, p.Ala564Val) in <jats:italic><jats:styled-content style=\"fixed-case\">VARS<\/jats:styled-content>2<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings emphasize the important complement of <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> and thorough clinical investigation in establishing precise clinical diagnosis. This approach constitutes the basis for personalized medicine in rare <jats:styled-content style=\"fixed-case\">IRD<\/jats:styled-content>s.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.14095","type":"journal-article","created":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T12:37:22Z","timestamp":1553863042000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The combination of whole\u2010exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies"],"prefix":"10.1111","volume":"97","author":[{"given":"Alaa","family":"Abu Diab","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Hadassah\u2010Hebrew University Medical Center Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ala'a","family":"AlTalbishi","sequence":"additional","affiliation":[{"name":"St John Eye Hospital Jerusalem 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