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Identification of Six Novel Mutations in ZEB1 and Description of the Associated Phenotypes in Patients with Posterior Polymorphous Corneal Dystrophy 3
Author(s) -
Evans Cerys J.,
Liskova Petra,
Dudakova Lubica,
Hrabcikova Pavlina,
Horinek Ales,
Jirsova Katerina,
Filipec Martin,
Hardcastle Alison J.,
Davidson Alice E.,
Tuft Stephen J.
Publication year - 2015
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12090
Subject(s) - keratometer , proband , ophthalmology , medicine , dioptre , corneal dystrophy , cornea , genetics , mutation , biology , visual acuity , gene
Summary Posterior polymorphous corneal dystrophy 3 (PPCD3) is a rare autosomal dominant disorder caused by mutations in ZEB1 . To date all identified disease‐causing variants were unique to the studied families, except for c.1576dup. We have detected six novel ZEB1 mutations; c.1749_1750del; p.(Pro584*) and c.1717_1718del; p.(Val573Phefs*12) in two Czech families, c.1176dup; p.(Ala393Serfs*19), c.1100C>A; p.(Ser367*), c.627del; p.(Phe209Leufs*11) in three British families and a splice site mutation, c.685–2A>G, in a patient of Sri Lankan origin. An additional British proband had the c.1576dup; p.(Val526Glyfs*3) mutation previously reported in other populations. Clinical findings were variable and included bilateral congenital corneal opacity in one proband, development of opacity before the age of 2 years in another individual and bilateral iris flocculi in yet another subject. The majority of eyes examined by corneal topography (10 out of 16) had an abnormally steep cornea (flat keratometry 46.5–52.7 diopters, steep keratometry 48.1–54.0 diopters). One proband underwent surgery for cryptorchidism. Our study further demonstrates that PPCD3 can present as corneal edema in early childhood, and that an abnormally steep keratometry is a common feature of this condition. As cryptorchidism has been previously observed in two other PPCD3 cases, its association with the disease warrants further investigation.