Identification of a possible association of JAK2 in development of microphthalmia, anophthalmia, and coloboma (MAC) complex in a child with 9p deletion and duplication

ABSTRACT

Background

Microphthalmia, anophthalmia, coloboma (MAC) complex is a spectrum of ocular abnormalities that occur in isolation or as part of a syndrome. Genetic abnormalities have been shown to account for 80% of cases in bilateral anophthalmia or severe microphthalmia, where 25–30% were attributed to chromosomal defects in this subset of MAC patients. To date, chromosome 9 short arm (9p) abnormalities have not been shown to associate with development of MAC.

Purpose

To report a case of MAC spectrum disorder that is related to 9p deletion and duplication.

Materials and Methods

A child who exhibited signs of MAC was evaluated retrospectively. Genetic analysis with comparative genomic hybridization (CGH) and a family pedigree was obtained from the proband.

Results

A 3-year-old girl with a history of an atrial septal defect, a horseshoe kidney and global developmental delay was presented. Ophthalmic examination revealed bilateral iris coloboma, bilateral choroidal-retinal coloboma, and left-sided microphthalmia. Subsequent oligonucleotide-based array CGH revealed two different sites of duplication and deletion on 9p (9p24.3 (209020_1143516)x1, 9p24.3p24.1 (1158662_6395264)x3).

Conclusion

We present the first case of MAC spectrum disorder that is related to 9p deletion and duplication. The link between the associated genetic abnormality and the phenotypic features is yet to be established. Duplication of JAK2 gene, which is within the same region of abnormalities, may have potentiated the development of MAC spectrum disease.

KEYWORDS:

• Microphthalmia
• anophthalmia
• coloboma
• MAC
• 9p
• JAK2

Contributors’ statement

Dr Kai Ching Peter, Leung designed, analysed, reviewed, and revised the manuscript. Dr Tak Chuen Simon, Ko revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.