Novel low-frequency maternal mosaicism mutation of <i>CHRDL1</i> gene resulted in the X-linked megalocornea in the offspring

Minh Phu Nguyen; Khanh Linh Nguyen; Quang Anh Pham; Huu Hong Thu Nguyen; Hai Ha Nguyen

doi:10.15625/vjbt-21531

Author affiliations

Authors

Minh Phu Nguyen \(^1\) Vietnam National Eye Hospital, 85 Ba Trieu, Hai Ba Trung, Hanoi, 10000, Vietnam.
Khanh Linh Nguyen \(^2\) Institute of Genome Research- Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 10000, Vietnam.
Quang Anh Pham \(^2\) Institute of Genome Research- Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 10000, Vietnam.
Huu Hong Thu Nguyen \(^2\) Institute of Genome Research- Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 10000, Vietnam.
Hai Ha Nguyen \(^2\) Institute of Genome Research- Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 10000, Vietnam.
\(^3\)Graduate University of Science and Technology- Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 10000, Vietnam. https://orcid.org/0000-0002-5431-5935

DOI:

https://doi.org/10.15625/vjbt-21531

Keywords:

megalocornea, anterior segment dysgenesis, CHRDL1 gene, whole exome sequencing, hemizygous variant

Abstract

X-linked megalocornea (MGC1) is an inherited disorder resulting from mutations of the CHRDL1 gene. Common symptoms of megalocornea include oversized cornea, deeper fluid-filled space between the cornea and iris, blurred or distorted vision at every distance, leading to mild vision issues. In this report, we present the first cases of megalocornea caused by the maternal low-frequency somatic mosaicism of the novel CHRDL1 mutation. Two Vietnamese siblings, 5 years old (MG001) and 13 years old (MG002) visited the hospital for regular check-ups with manifestations such as myopic, exophthalmia, and enlarged cornea. They were suspected of having inherited megalocornea disorder without glaucoma symptoms. The DNA genome of the proband (MG001) was applied for whole exome sequencing (WES) analysis, and the result revealed a hemizygous pathogenic variant c.943dupA in the CHRDL1 gene, which results in a frameshift mutation (p.Ile315fs) in protein. This mutation was also identified in the proband (MG002) by Sanger sequencing. Notably, the CHRDL1 c.943dupA mutation was recognized at a very low fraction in the maternal DNA after triplicate Sanger sequencing, indicating that the mother has a mosaicism mutation of CHRDL1 c.943dupA. This study reported a rare case of X-linked megalocornea in a family and provides a novel genetic factor relating to an eye disorder in Vietnam.

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