TY - JOUR
T1 - First reported case of Doyne honeycomb retinal dystrophy (Malattia Leventinese/autosomal dominant drusen) in Scandinavia
AU - Sheyanth, Inger Norlyk
AU - Lolas, Ihab Bishara
AU - Okkels, Henrik
AU - Kiruparajan, Ligor Pradeep
AU - Abildgaard, Søren Kromann
AU - Petersen, Michael Bjørn
N1 - © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
PY - 2021/4
Y1 - 2021/4
N2 - BACKGROUND: Doyne honeycomb retinal dystrophy (DHRD)/malattia leventinese (ML) is an autosomal dominant, progressive retinal disorder characterized by massive central retinal drusen often partly coalescent forming a characteristic honeycomb-like pattern. Debut of vision loss often occurs in early to mid-adulthood, and the degree varies. A single variant in EFEMP1: c.1033C>T (R345W) has been identified as the cause in all cases.METHODS: Following DNA isolation, exome sequencing was performed in seven genes associated with flecked retina. Direct sequencing was used for variant verification.RESULTS: We report the first Scandinavian case of molecular genetically verified DHRD/ML: a 57-year-old woman debuting with vision loss and metamorphopsia. On both eyes, ophthalmological findings included massive hard drusen in the macular region and nasal to the optic disc as well as macular hyperpigmentation. Secondary choroidal neovascularizations were identified on both eyes, and anti-vascular endothelial growth factor was administered, without effect.CONCLUSION: Molecular genetic investigation revealed heterozygosity for the known pathogenic missense variant in EFEMP1: c.1033C>T (R345W) previously reported in relation to DHRD/ML. Family history revealed no other cases of similar visual impairment suggesting a de novo mutation. Furthermore, there was no correlation between the unique DHRD/ML haplotypes reported in the literature and our patient.
AB - BACKGROUND: Doyne honeycomb retinal dystrophy (DHRD)/malattia leventinese (ML) is an autosomal dominant, progressive retinal disorder characterized by massive central retinal drusen often partly coalescent forming a characteristic honeycomb-like pattern. Debut of vision loss often occurs in early to mid-adulthood, and the degree varies. A single variant in EFEMP1: c.1033C>T (R345W) has been identified as the cause in all cases.METHODS: Following DNA isolation, exome sequencing was performed in seven genes associated with flecked retina. Direct sequencing was used for variant verification.RESULTS: We report the first Scandinavian case of molecular genetically verified DHRD/ML: a 57-year-old woman debuting with vision loss and metamorphopsia. On both eyes, ophthalmological findings included massive hard drusen in the macular region and nasal to the optic disc as well as macular hyperpigmentation. Secondary choroidal neovascularizations were identified on both eyes, and anti-vascular endothelial growth factor was administered, without effect.CONCLUSION: Molecular genetic investigation revealed heterozygosity for the known pathogenic missense variant in EFEMP1: c.1033C>T (R345W) previously reported in relation to DHRD/ML. Family history revealed no other cases of similar visual impairment suggesting a de novo mutation. Furthermore, there was no correlation between the unique DHRD/ML haplotypes reported in the literature and our patient.
KW - Doyne honeycomb retinal dystrophy
KW - EFEMP1
KW - Malattia leventinese
UR - http://www.scopus.com/inward/record.url?scp=85102263080&partnerID=8YFLogxK
U2 - 10.1002/mgg3.1652
DO - 10.1002/mgg3.1652
M3 - Journal article
C2 - 33689237
SN - 2324-9269
VL - 9
JO - Molecular Genetics & Genomic Medicine
JF - Molecular Genetics & Genomic Medicine
IS - 4
M1 - e1652
ER -