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New mutations in GJA8 expand the phenotype to include total sclerocornea
Author(s) -
Ma A.S.,
Grigg J.R.,
Prokudin I.,
Flaherty M.,
Bennetts B.,
Jamieson R.V.
Publication year - 2018
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13045
Subject(s) - microphthalmia , proband , biology , phenotype , genetics , mutation , cataracts , abnormality , gene , medicine , psychiatry
This project expands the disease spectrum for mutations in GJA8 to include total sclerocornea, rudimentary lenses and microphthalmia, in addition to this gene's previously known role in isolated congenital cataracts. Ophthalmic findings revealed bilateral total sclerocornea in 3 probands, with small abnormal lenses in 2 of the cases, and cataracts and microphthalmia in 1 case. Next‐generation sequencing revealed de novo heterozygous mutations affecting the same codon of GJA8 : (c. 281G >A; p.( Gly94Glu ) and c. 280G >C; p.( Gly94Arg )) in 2 of the probands, in addition to the c. 151G >A; p.( Asp51Asn ) mutation we had previously identified in the third case. In silico analysis predicted all of the mutations to be pathogenic. These cases show that deleterious, heterozygous mutations in GJA8 can lead to a severe ocular phenotype of total sclerocornea, abnormal lenses, and/or cataracts with or without microphthalmia, broadening the phenotype associated with this gene. GJA8 should be included when investigating patients with the severe anterior segment abnormality of total sclerocornea.