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

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.