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Brief Report |

Expanding the Phenotype of TRNT1-Related Immunodeficiency to Include Childhood Cataract and Inner Retinal Dysfunction

Sarah Hull, MA, FRCOphth1,2; Aeesha N. J. Malik, MRCP, FRCOphth2; Gavin Arno, PhD1,2; Donna S. Mackay, PhD3; Vincent Plagnol, MSc, PhD4; Michel Michaelides, MD(Res), FRCOphth1,2; Sahar Mansour, BMBS, FRCP5; Assunta Albanese, MD(Res), FRCPCH6; Katrina Tatton Brown, BM BCh, MD(Res)5; Graham E. Holder, MSc, PhD1,2; Andrew R. Webster, MD(Res), FRCOphth1,2; Paul T. Heath, FRACP, FRCPCH6; Anthony T. Moore, MA, FRCOphth1,2,7
[+] Author Affiliations
1Institute of Ophthalmology, University College London, London, England
2Moorfields Eye Hospital, London, England
3Department of Ophthalmology and Visual Sciences, Washington University in St Louis, St Louis, Missouri
4Genetics Institute, University College London, London, England
5Medical Genetics Unit, St George’s University of London, London, England
6Paediatric Infectious Diseases Unit, St George’s Hospital, London, England
7Department of Ophthalmology, University of California, San Francisco
JAMA Ophthalmol. 2016;134(9):1049-1053. doi:10.1001/jamaophthalmol.2015.5833.
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Importance  A multiorgan syndromic disorder characterized by sideroblastic anemia, immunodeficiency, periodic fever, and developmental delay with an uncharacterized retinal dystrophy is caused by TRNT1. This report of a family with a homozygous mutation in TRNT1 expands the ocular phenotype to include cataract and inner retinal dysfunction and details a mild systemic phenotype.

Observations  A consanguineous family with 3 affected children was investigated. Key clinical features comprised hypogammaglobulinemia, short stature with microcephaly, cataract, and inner retinal dysfunction without sideroblastic anemia or developmental delay. Two siblings had poor balance and 1 sibling had sensorineural hearing loss. The oldest sibling had primary ovarian failure diagnosed at age 14.5 years. Exome sequencing identified a homozygous missense variant in TRNT1, c.295C>T (p.Arg99Trp) in all 3 patients. The sibling with hearing loss also harbored a homozygous mutation in GJB2, c.71G>A (p.Trp24*), which is an established cause of sensorineural hearing loss.

Conclusions and Relevance  This family expands the ocular and systemic phenotypes associated with mutations in TRNT1, demonstrating phenotypic variability and highlighting the need for ophthalmic review of these patients.

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Figure 1.
Anterior Segment Photographs of Cataracts in All Patients

Patient 1, cortical spoke-like cataract; patient 2, posterior subcapsular cataract; and patient 3, white nuclear cataract (measurement scale not available).

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Figure 2.
Electroretinogram (ERG) and Pattern ERG (PERG) of the Right Eyes of the 3 Siblings, With a Normal Eye (N) for Comparison

The findings are consistent with relatively severe generalized inner retinal dysfunction, with severe macular dysfunction demonstrated in patient 1. Dark-adapted (DA) and lighted-adapted (LA) stimulus strength was measured in candela-seconds per meter squared. For DA 0.01, DA 10.0, and LA 3.0, there is a 10-millisecond (ms) prestimulus delay.

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