Sir,

The anoctamin (ANO) family consists of 10 members, many of which have been found to be calcium-activated chloride channels (CaCC).1, 2, 3 Recessive mutations in anoctamin 5 (ANO5) result in a proximal limb-girdle muscular dystrophy (LGMD2L).2, 3 ANO5 is mostly expressed in the skeletal tissue in humans,2, 4 but transcripts have been identified in the retinal pigment epithelium (RPE)/choroid and fetal eye.4

The present report describes an association between LGMD2L consequent upon mutation in ANO5 and macular dystrophy in one affected person.

Case report

A 71-year-old man was referred after persistent left eye distortion after uncomplicated cataract surgery. He was known to be affected by LGMD2L, having presented with proximal muscle weakness in his early 40 s. There was no history of retinotoxic medication. He had a 5-year history of type-2 diabetes and was a moderate smoker (20 cigarettes/day). One older brother out of nine siblings was similarly affected with symptoms and signs consistent with adult LGMD, which presented at the age of 44 years. He had no ophthalmic complaints and was an ex-smoker of 6 years. No other relatives were known to have either muscular dystrophy or retinal disease.

Visual acuities (VAs) were 6/9 right, 6/12 left. Ishihara colour test was 5/17 right, 1/17 left. Imaging revealed parafoveal atrophic hypoautofluorescent patches in both maculae (Figures 1c and d). Spectral domain optical coherence tomography (SD-OCT) appears in Figures 1e and f. Pattern electroretinograms (ERGs) were abnormal and multifocal ERG revealed parafoveal dysfunction (Figure 2b). Full-field ERGs (Figure 2a) and electrooculography were normal. The PRPH2/RDS gene showed a normal coding sequence.

Figure 1
figure 1

Colour fundus photographs of the index case show bilateral macular symmetrical atrophic chorioretinal patches, OD (a) and OS (b) with no apparent flecks or drusen; which are hypoautofluorescent, OD (c) and OS (d) and correspond to areas of retinal atrophy and ellipsoid layer disruption on SD-OCT, OD (e) and OS (f). His sibling’s autofluorescence shows no abnormality, OD (g) and OS (h); SD-OCT shows bilateral epiretinal membranes with diffuse retinal thickening, OD (i) and OS (j).

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Figure 2
figure 2

Electrophysiology of affected individual. (a) ISCEV standard full-field ERGs show no significant abnormalities for age. Pattern ERGs (PERGs) are bilaterally subnormal and delayed, but with reasonable amplitude increase with a larger field (30°). (b) Multifocal ERGs (mfERG) show relative preservation of the response to the central foveal hexagon with significant loss of amplitude in immediate parafoveal responses, right eye worse than left (DA, dark adapted; LA, light-adapted; PERG, pattern electroretinogram. 0.01, 11.0. 3.0 are light intensities measured in cd.s.m−2) .

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Sanger sequencing of exons 1–22 of the ANO5 gene showed homozygosity for c.191dupA, p.(N64KfsX15) in exon 5, which, if expressed would lead to a peptide missing the carboxyl 850 of its 913 amino acids. The 78-year-old affected brother had VAs of 6/9 right, 6/6 left, with bilateral epiretinal membranes (Figures 1i and j). Autofluorescence was normal (Figures 1g and h).

Comment

The index case maculopathy is unlike that seen in age-related macular disease, or in known mendelian dystrophies and probably represents a novel late-onset macular dystrophy. ANO5 is expressed in the human RPE/choroid4 and although its exact function remains unknown, it is thought to encode a CaCC.1, 2 CaCCs have a physiological role in RPE, important for fluid and ion transport across the RPE.1, 5, 6

To the best of our knowledge this is the first report regarding this association.

Although the possibility of the coincidence of two rare disorders in the proband cannot be excluded, the data are consistent with the occurrence of retinal macular disease in ANO5-mediated muscular dystrophy in some, but not all, mutation carriers.