Ophthalmic genetics · 2026
Homozygous R383H variant in IDUA gene causing pericentric retinitis pigmentosa in attenuated mucopolysaccharidosis type I.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Chattannavar Goura, Sadhu Pravalika, Jalali Subhadra, Kekunnaya Ramesh
Аннотация
INTRODUCTION: Biallelic variants in the IDUA gene are linked to Mucopolysaccharidosis type I (MPS I), a rare type I lysosomal storage disorder characterized by systemic manifestations of coarse facies, macrocephaly, hepatosplenomegaly, dysostosis multiplex, hearing loss, cardiac issues, airway involvement, hydrocephalus, and intellectual disability. Based on the age at which symptoms appear and the degree of intellectual impairment, MPS I can be categorized into Hurler, Hurler-Scheie, and Scheie syndromes.
METHODS: Here, we describe a patient with congenital onset familial dyschromatopsia, adult-onset pericentric retinitis pigmentosa, and cardiac valve disease requiring surgery.
RESULTS: Retinitis pigmentosa panel testing showed a heterozygous pathogenic variant in ABCA4 (c.6729+5_6729+19del) gene and a heterozygous variant of uncertain significance (VUS) in AHI1 (c. 2971C>T, p. Arg991Cys) gene. Later, whole exome sequencing revealed a homozygous pathogenic variant in IDUA: c.1148G>A, p. Arg383His (R383H) and a pathogenic 35kb deletion of Xq28 (153418413_153453555) encompassing OPN1LW, TEX28P2, and OPN1LM gene. Iduronidase enzyme activity in blood leukocytes was 0.06 nmol/h/mg Prot (normal ≥2.06 nmol/h/mg Prot). The urine glycosaminoglycans were 23.7 mg/mmol of creatinine (normal <3.1 mg/mmol of creatinine).
CONCLUSIONS: The homozygous variant of R383H in IDUA gene presents with attenuated MPS I with adult-onset retinitis pigmentosa and reduced iduronidase activity. Enzyme activity helps in interpreting genetic results, especially when there are multiple variants in different genes causing a similar phenotype, guiding appropriate systemic evaluation. This case also highlights the need for broader genetic testing when small panel results are negative despite a strong clinical phenotype.
METHODS: Here, we describe a patient with congenital onset familial dyschromatopsia, adult-onset pericentric retinitis pigmentosa, and cardiac valve disease requiring surgery.
RESULTS: Retinitis pigmentosa panel testing showed a heterozygous pathogenic variant in ABCA4 (c.6729+5_6729+19del) gene and a heterozygous variant of uncertain significance (VUS) in AHI1 (c. 2971C>T, p. Arg991Cys) gene. Later, whole exome sequencing revealed a homozygous pathogenic variant in IDUA: c.1148G>A, p. Arg383His (R383H) and a pathogenic 35kb deletion of Xq28 (153418413_153453555) encompassing OPN1LW, TEX28P2, and OPN1LM gene. Iduronidase enzyme activity in blood leukocytes was 0.06 nmol/h/mg Prot (normal ≥2.06 nmol/h/mg Prot). The urine glycosaminoglycans were 23.7 mg/mmol of creatinine (normal <3.1 mg/mmol of creatinine).
CONCLUSIONS: The homozygous variant of R383H in IDUA gene presents with attenuated MPS I with adult-onset retinitis pigmentosa and reduced iduronidase activity. Enzyme activity helps in interpreting genetic results, especially when there are multiple variants in different genes causing a similar phenotype, guiding appropriate systemic evaluation. This case also highlights the need for broader genetic testing when small panel results are negative despite a strong clinical phenotype.