Akademik Veri Yönetim Sistemi
15.Ulusal Tıbbi Genetik Kongresi, Muğla, Türkiye, 9 - 13 Kasım 2022, ss.269
INTRODUCTION: Ocular coloboma refers to a defect that affects all or part of the iris, lens,
choroid, retina, and optic nerve that result from the failure of closure of the optic fissure. It
occurs in 0.5-2.2/10,000. Microphthalmia is characterized by a reduced axial length of the eye.
The precise pathogenesis of microphthalmia hasn’t been clarified yet. It occurs in 0.2-
1.7/10,000. Coloboma and Microphthalmia may occur together, unilateral or bilateral, and
isolated or as part of a syndromic condition. ATP binding-cassette-subfamily-B-member6(ABCB6) encodes a member of the ATP-binding-cassette transporter superfamily. Mutations
in ABCB6 underlie autosomal dominant isolated colobomatous microphthalmia-7
(MCOPCB7). Here we present the first case of MCOPCB7 due to ABCB6 gene mutation in
Turkey and the first nonsense mutation in this gene reported in the literature. CASE: 3-monthsold female patient, was referred to our clinic with bilateral iris coloboma, fundus coloboma
including optic disc and macula, and microphthalmic left eye. There were no additional
dysmorphic features, and neurological, cardiovascular, genitourinary system examination and
renal ultrasound were found to be normal which ruled out CHARGE syndrome. She was the
3rd child of the family. Her siblings and parents were healthy and the parents were nonconsanguineous. METHOD and RESULT: Peripheral blood sample was used for DNA
isolation and karyotype analysis. She had a 46, XX normal female karyotype. Array-cgh
performed after karyotype analysis showed a 91.8 Kb heterozygous deletion of chromosome
9p21.2, which doesn’t contain any genes and doesn’t seem like the cause of the condition.
Afterward, Whole-Exome-Sequencing (WES) was performed using the xGen-ExomeResearch-Panel-v2 kit. We detected a heterozygous stop-gain (nonsense) variant (c.1216C>T;
p.R406*) on exon 6 of ABCB6. It is classified as “Likely Pathogenic” according to the ACMG
Classification. DISCUSSION: Colobomatous microphthalmia (C/M) is a rare developmental
disorder of the eye, found in numerous heritable syndromes but also occurs in isolation.
Molecular diagnosis is challenging as the genes associated to date with C/M account for only a
small percentage of cases. Overall, the genetic cause remains unknown in up to 80% of patients.
Autosomal dominant, recessive, and X-linked inheritance and mutations in 11 genes (TENM3,
SHH, GDF6, RBP4, GDF3, VSX2, MCOPCB2, STRA6, MCOPCB1, MCOPCB4, ABCB6)
have been identified, implicating of genetic heterogeneity in isolated C/M. In the ABCB6 gene,
18 pathogenic, and 5 likely pathogenic variants reported in databases thus far. None of them is
nonsense. The nonsense variant we reported, has already been found in dbSNP, however, hasn’t
been reported in any article yet. Despite the lack of causal treatment for C/M, knowledge of the
underlying genetic cause in patients is highly important for managing ocular and possibly
associated syndromic conditions, confirmation of the clinical diagnosis, and guiding genetic
counseling. Genetic testing is also may help elucidate the cellular and molecular basis of C/M,
which may prompt the development of potential therapies and lead to the identification of new
causal genes. Herein, it is important that patients are consulted more frequently to the Medical
Genetics department and advanced genetic analysis methods such as WES become widespread.