Scholarlink

Purpose <p>To report the clinical phenotype, imaging characteristics, and electrophysiologic findings of a 62-year-old patient with retinitis pigmentosa (RP) harboring a likely pathogenic homozygous <i>KIZ</i> (NM_018474.6) start codon variant (c.3G &gt; A, p.Met1?), only previously reported in the compound heterozygous state.</p> Methods <p>The patient underwent clinical evaluation including full medical history, best-corrected visual acuity (BCVA), slit lamp exam, and dilated fundus examination (DFE), spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and full-field electroretinography (ffERG), following the ISCEV standard protocols. Genetic testing was performed using the Invitae inherited retinal disorders panel of 330 genes.</p> Results <p>BCVA was 20/40 in both eyes. Fundus examination revealed mild optic disc pallor, arteriolar attenuation, peripheral pigment migration, and macular hyper-autofluorescence along the arcades. with macular sparing. Outside the arcades, there are hypo-autofluorescence spots corresponding to retinal pigement epithelium atrophy. There is marked peri-papillary atrophy. SD-OCT showed diffuse outer retinal thinning, ellipsoid zone constriction, mild cystoid macular edema, and epiretinal membrane. ffERG was consistent with a rod-cone dystrophy, with extinguished dark-adapted responses and severely attenuated 30&#xa0;Hz flicker amplitudes. Genetic testing identified a heterozygous variant of uncertain significance in CTNNA1 (c.1486C &gt; T, p.Arg496Cys) and a homozygous <i>KIZ</i> variant (c.3G &gt; A, p.Met1?), previously observed only in compound heterozygosity. The patient was diagnosed with <i>KIZ</i>-associated RP and initiated on topical dorzolamide.</p> Conclusions <p>This case expands the clinical spectrum of <i>KIZ</i>-associated RP by describing the phenotype associated with a homozygous start codon variant. Despite the disruptive nature of the mutation, the patient exhibited a relatively mild rod-cone dystrophy with retained cone responses into the seventh decade. These findings support the inclusion of <i>KIZ</i> in diagnostic panels for autosomal recessive RP and contribute valuable genotype–phenotype correlation data for this rare ciliopathy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Retained cone-responses in homozygous start codon variant in KIZ-associated retinitis pigmentosa

  • 期刊论文

  • 发表日期：

    2026年1月20日

查看全文
  • Maximilian D. Kong,
  • Mia O’Connell,
  • Abdhel Exinor,
  • Megan Soucy,
  • Scott E. Brodie,
  • Stephen H. Tsang

摘要

Purpose

To report the clinical phenotype, imaging characteristics, and electrophysiologic findings of a 62-year-old patient with retinitis pigmentosa (RP) harboring a likely pathogenic homozygous KIZ (NM_018474.6) start codon variant (c.3G > A, p.Met1?), only previously reported in the compound heterozygous state.

Methods

The patient underwent clinical evaluation including full medical history, best-corrected visual acuity (BCVA), slit lamp exam, and dilated fundus examination (DFE), spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and full-field electroretinography (ffERG), following the ISCEV standard protocols. Genetic testing was performed using the Invitae inherited retinal disorders panel of 330 genes.

Results

BCVA was 20/40 in both eyes. Fundus examination revealed mild optic disc pallor, arteriolar attenuation, peripheral pigment migration, and macular hyper-autofluorescence along the arcades. with macular sparing. Outside the arcades, there are hypo-autofluorescence spots corresponding to retinal pigement epithelium atrophy. There is marked peri-papillary atrophy. SD-OCT showed diffuse outer retinal thinning, ellipsoid zone constriction, mild cystoid macular edema, and epiretinal membrane. ffERG was consistent with a rod-cone dystrophy, with extinguished dark-adapted responses and severely attenuated 30 Hz flicker amplitudes. Genetic testing identified a heterozygous variant of uncertain significance in CTNNA1 (c.1486C > T, p.Arg496Cys) and a homozygous KIZ variant (c.3G > A, p.Met1?), previously observed only in compound heterozygosity. The patient was diagnosed with KIZ-associated RP and initiated on topical dorzolamide.

Conclusions

This case expands the clinical spectrum of KIZ-associated RP by describing the phenotype associated with a homozygous start codon variant. Despite the disruptive nature of the mutation, the patient exhibited a relatively mild rod-cone dystrophy with retained cone responses into the seventh decade. These findings support the inclusion of KIZ in diagnostic panels for autosomal recessive RP and contribute valuable genotype–phenotype correlation data for this rare ciliopathy.