Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects. (6th January 2015)

• Record Type: Journal Article
• Authors: Slavotinek, A.M.; Garcia, S.T.; Chandratillake, G.; Bardakjian, T.; Ullah, E.; Wu, D.; Umeda, K.; Lao, R.; Tang, P.L.‐F.; Wan, E.; Madireddy, L.; Lyalina, S.; Mendelsohn, B.A.; Dugan, S.; Tirch, J.; Tischler, R.; Harris, J.; Clark, M.J.; Chervitz, S.; Patwardhan, A.; West, J.M.; Ursell, P.; de Alba Campomanes, A.; Schneider, A.; Kwok, P.‐y.; Baranzini, S.; Chen, R.O.
• Is Part Of: Clinical genetics. Volume 88:Number 5(2015:Nov.)
• Page Start: 468
• Page End: 473
• Publication Date: 2015-01-06
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12543
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12543-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12543-para-0001">Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing with the ACE Exome<sup>TM</sup> (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 cases) to sequence 28 patients with A/M and four patients with varied developmental eye defects. In the 28 patients with A/M, we identified <italic>de novo</italic> mutations in three patients (<italic>OTX2</italic>, p.(Gln91His), <italic>RARB</italic>, p.Arg387Cys and <italic>GDF6</italic>, p.Ala249Glu) and inherited mutations in <italic>STRA6</italic> in two patients. In patients with developmental eye defects, a female with cataracts and cardiomyopathy had a <italic>de novo COL4A1</italic> mutation, p.(Gly773Arg), expanding the phenotype associated with <italic>COL4A1</italic> to include cardiomyopathy. A male with a chorioretinal defect, microcephaly, seizures and sensorineural deafness had two <italic>PNPT1</italic> mutations, p.(Ala507Ser) and c.401‐1G>A, and we describe eye defects associated with this gene for the first time. Exome sequencing was efficient for identifying mutations in pathogenic genes for which there is no clinical testing available and for identifying cases that expand phenotypic spectra, such as the <italic>PNPT1</italic> and <italic>COL4A1</italic>‐associated disorders described here.</p> </abstract>