September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
RARB mutations presenting with variable clinical features in patients with microphthalmia, anophthalmia, and/or coloboma (MAC): A Case Series.
Author Affiliations & Notes
  • Prashanth Iyer
    Christiana Care Health Systems, Newark, Delaware, United States
  • Nutsuchar Wangtiraumnuay
    Department of Pediatric Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania, United States
  • Sarina Kopinsky
    Genetics Division, Einstein Medical Center, Philadelphia, Pennsylvania, United States
  • Jenina Capasso
    Department of Pediatric Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania, United States
  • Bing Chiu
    Christiana Care Health Systems, Newark, Delaware, United States
  • Venkatesh Brahma
    Christiana Care Health Systems, Newark, Delaware, United States
  • Alex V Levin
    Department of Pediatric Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania, United States
  • Adele Schneider
    Genetics Division, Einstein Medical Center, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Prashanth Iyer, None; Nutsuchar Wangtiraumnuay , None; Sarina Kopinsky, None; Jenina Capasso , None; Bing Chiu, None; Venkatesh Brahma, None; Alex Levin, None; Adele Schneider, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 668. doi:
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      Prashanth Iyer, Nutsuchar Wangtiraumnuay, Sarina Kopinsky, Jenina Capasso, Bing Chiu, Venkatesh Brahma, Alex V Levin, Adele Schneider; RARB mutations presenting with variable clinical features in patients with microphthalmia, anophthalmia, and/or coloboma (MAC): A Case Series.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):668.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The retinoid acid receptor beta (RARB) gene is involved in eye development through the vitamin A pathway, and mutations in RARB have been shown to cause MAC (microphthalmia, anophthalmia and/or coloboma) via both dominant and recessive modes of inheritance. Besides MAC, RARB is also associated with features of PDAC (pulmonary hypoplasia, diaphragmatic hernia, anophthalmia/MAC, and cardiac defects). We report three patients with autosomal dominant mutations in RARB and compare their clinical presentations to understand the mechanism of RARB.

Methods : This is a retrospective case series looking at the clinical features present in three patients with microphthalmia, anophthalmia and/or coloboma, and analyzing and comparing their results on whole exome sequencing.

Results : The mutation in patient #2 is novel and previously unpublished. Patients #1 and #2 have nearly identical missense mutations in RARB. Patient #1 has a missense mutation, c.1159C>T, predicting p.R387C (Arginine to Cysteine at the 387th position). Patient #2 has a mutation, c.1160G>T, predicting p.R387L (Arginine to Leucine at the 387th position). Clinically, patient #1 presents with bilateral microphthalmia, coloboma, pulmonary hypoplasia, diaphragmatic hernia, and cardiac pathology, whereas patient #2 has bilateral microphthalmia and developmental delay without PDAC, despite the similarity in their genetic mutations. Patient #3 has a de novo, missense mutation of the RARB gene, c.658T>C, predicting p.L213P (leucine to proline at 213), at an earlier position in the gene as compared to the mutations in the other patients. She presents clinically with bilateral microphthalmia, coloboma, intestinal malrotation and cardiac disease.

Conclusions : It is unclear why dominant RARB mutations similar in nature would have such different clinical presentations. Possible explanations include protein folding differences, other genes that could modify RARB function, and vitamin A levels in utero that could modify expression of RARB. These three patients highlight the shift from genetics to genomics, as we seek to understand epigenetic interactions and to identify environmental factors that might potentially be manipulated for patients with specific genotypes.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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