Missense mutation in SLIT2 associated with congenital myopia, anisometropia, connective tissue abnormalities, and obesity

Katherine Y Liu; Jesse D Sengillo; Gabriel Velez; Ruben Jauregui; Lynn Y Sakai; Irene H Maumenee; Alexander G Bassuk; Vinit B Mahajan; Stephen H Tsang

doi:10.1186/s13023-018-0885-4

Missense mutation in SLIT2 associated with congenital myopia, anisometropia, connective tissue abnormalities, and obesity

Orphanet J Rare Dis. 2018 Aug 15;13(1):138. doi: 10.1186/s13023-018-0885-4.

Authors

Katherine Y Liu¹, Jesse D Sengillo^{2

3}, Gabriel Velez^{4

5

6}, Ruben Jauregui^{2

7}, Lynn Y Sakai⁸, Irene H Maumenee², Alexander G Bassuk⁹, Vinit B Mahajan^{4

5

10}, Stephen H Tsang^{11

12

13

14}

Affiliations

¹ Stony Brook University School of Medicine, Stony Brook, NY, USA.
² Department of Ophthalmology, Columbia University, New York, NY, USA.
³ Department of Medicine, Reading Hospital, West Reading, PA, USA.
⁴ Omics Laboratory, Stanford University, Palo Alto, CA, USA.
⁵ Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USA.
⁶ Medical Scientist Training Program, University of Iowa, Iowa City, IA, USA.
⁷ Weill Cornell Medical College, New York, NY, USA.
⁸ Departments of Molecular and Medical Genetics and Biochemistry and Molecular Biology, Oregon Health and Science University and Shriners Hospital for Children, Portland, USA.
⁹ Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
¹⁰ Palo Alto Veterans Administration, Palo Alto, CA, USA.
¹¹ Jonas Children's Vision Care, and Bernard and Shirlee Brown Glaucoma Laboratory, New York, USA. gene.editing@gmail.com.
¹² Department of Ophthalmology, Columbia University, New York, NY, USA. gene.editing@gmail.com.
¹³ Department of Pathology and Cell Biology, Stem Cell Initiative (CSCI), Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA. gene.editing@gmail.com.
¹⁴ Harkness Eye Institute, Columbia University Medical Center, 635 West 165th Street, Box 212, New York, NY, 10032, USA. gene.editing@gmail.com.

Abstract

Background: SLIT2 is a protein ligand for the Roundabout (ROBO) receptor and was found to play a major role in repulsive midline axon guidance in central nervous system development. Based on studies utilizing knockout models, it has been postulated that SLIT2 is important for preventing inappropriate axonal routing during mammalian optic chiasm development.

Methods: Case report.

Results: Here, we report a case of congenital myopia, anisometropia, and obesity in a patient with a SLIT2 point mutation. Examination of the patient's skin biopsy revealed abnormalities in elastin and collagen fibrils that suggest an underlying connective tissue disorder. Structural modeling placed the novel mutation (p.D1407G) in the EGF-like domain 8 and was predicted to affect interactions with SLIT2 binding partners.

Conclusions: To the authors' knowledge, this is the first report of a SLIT2 variant in the context of these ocular findings.

Keywords: Anisometropia; Myopia; Obesity; Precision medicine; SLIT2; Structural modeling.

Publication types

Case Reports
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Anisometropia / genetics*
Connective Tissue Diseases / genetics*
Humans
Intercellular Signaling Peptides and Proteins / genetics*
Male
Mutation, Missense / genetics*
Nerve Tissue Proteins / genetics*
Obesity / genetics*

Substances

Intercellular Signaling Peptides and Proteins
Nerve Tissue Proteins
Slit homolog 2 protein

Abstract

Publication types

MeSH terms

Substances

Grants and funding