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Oculocutaneous albinism type 7 (OCA7) is an autosomal recessive ocular hypopigmentation disorder caused by biallelic variants in LRMDA, characterized by severe foveal hypoplasia, chiasmal misrouting and impaired visual acuity but minimal skin or hair involvement. The gene LRMDA encodes a melanocyte differentiation factor and is listed as HGNC:23405. The disorder is catalogued in Monarch as Oculocutaneous Albinism Type 7.
A recent study described three new OCA7 patients—two siblings from a consanguineous Kurdish family and one unrelated Dutch individual—bringing the total to 18 reported patients with LRMDA‐related OCA7 ([PMID:38555393]). All cases exhibited autosomal recessive inheritance with homozygous or compound heterozygous variants and segregation confirmed in the consanguineous pedigree. Twenty probands across 18 kindreds now define the core genetic cohort for OCA7 ([PMID:38555393]).
Genetic analysis has identified primarily missense variants in LRMDA; the sole novel variant reported is c.565G>A (p.Gly189Ser) ([PMID:38555393]). No clear truncating or splice‐site alleles have been recurrently observed, and no founder variants have been described to date. Variant interpretation has relied on ACMG criteria and in silico predictions in the absence of functional assays.
Phenotypically, all patients shared severely reduced visual acuity (0.4–1.3 logMAR), nystagmus, hypopigmentation of the fundus, severe foveal hypoplasia and chiasmal misrouting, with normal skin and hair pigmentation and no iris translucency ([PMID:38555393]). These ocular manifestations resemble X‐linked ocular albinism and suggest a melanocyte‐specific impact of LRMDA variants on retinal development.
Functional evidence for LRMDA pathogenicity remains limited: no dedicated cellular or animal models have been reported, and the role of LRMDA in melanosome biogenesis or retinal pigment epithelium differentiation is inferred but untested. Existing large‐scale OCA gene screens confirm the rarity of LRMDA variants in broader cohorts but do not include functional follow‐up.
Collectively, the genetic data support a Moderate level of evidence for a causal relationship between LRMDA and OCA7, with segregation in a consanguineous family and consistent phenotype across 18 patients. Functional studies are needed to clarify mechanism. Key take-home: LRMDA sequencing should be included in diagnostic panels for autosomal recessive ocular albinism to guide genetic counseling and potential future therapeutic development.
Gene–Disease AssociationModerate18 unrelated patients (including 3 novel cases) with biallelic LRMDA variants, segregation in a consanguineous family and highly consistent ocular phenotype ([PMID:38555393]) Genetic EvidenceModerateAutosomal recessive inheritance in 18 probands, segregation confirmed in one pedigree, one novel missense variant c.565G>A (p.Gly189Ser) characterized Functional EvidenceLimitedNo dedicated functional assays or in vivo models reported; pathogenicity inferred solely from genetic and phenotype correlation |