Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy in a Chinese Family With Mutation of the Efemp1 Gene

Zhang, Ting; Xie, Xuelu; Cao, Guiqun; Jiang, Haiou; Wu, Sisi; Su, Zhiguang; Zhang, Kang; Lu, Fang

doi:10.1097/iae.0000000000000259

Cited by 14 publications

(7 citation statements)

References 23 publications

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“…Previous ocular genetic studies have identified a recurrent, missense mutation in exon-10 of EFEMP1 (c.1033C>T, p.R345W) associated with Doyne honeycomb retinal dystrophy (DHRD) and/or Malattia Leventinese (MLVT, MIM: 126600) in European and Asian families [ 11 , 20 – 24 ]. Recently, a novel intronic variant of unknown significance in EFEMP1 was reported in a DHRD patient [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing Identifies a Missense Variant in EFEMP1 Co-Segregating in a Family with Autosomal Dominant Primary Open-Angle Glaucoma

2015

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Primary open-angle glaucoma (POAG) is a clinically important and genetically heterogeneous cause of progressive vision loss as a result of retinal ganglion cell death. Here we have utilized trio-based, whole-exome sequencing to identify the genetic defect underlying an autosomal dominant form of adult-onset POAG segregating in an African-American family. Exome sequencing identified a novel missense variant (c.418C>T, p.Arg140Trp) in exon-5 of the gene coding for epidermal growth factor (EGF) containing fibulin-like extracellular matrix protein 1 (EFEMP1) that co-segregated with disease in the family. Linkage and haplotype analyses with microsatellite markers indicated that the disease interval overlapped a known POAG locus (GLC1H) on chromosome 2p. The p.Arg140Trp substitution was predicted in silico to have damaging effects on protein function and transient expression studies in cultured cells revealed that the Trp140-mutant protein exhibited increased intracellular accumulation compared with wild-type EFEMP1. In situ hybridization of the mouse eye with oligonucleotide probes detected the highest levels of EFEMP1 transcripts in the ciliary body, cornea, inner nuclear layer of the retina, and the optic nerve head. The recent finding that a common variant near EFEMP1 was associated with optic nerve-head morphology supports the possibility that the EFEMP1 variant identified in this POAG family may be pathogenic.

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Section: Discussionmentioning

confidence: 99%

Exome Sequencing Identifies a Missense Variant in EFEMP1 Co-Segregating in a Family with Autosomal Dominant Primary Open-Angle Glaucoma

2015

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“…Secondly, besides remarkable drusen, there were large dark gray lesions originated from RPE/choroid atrophy in the posterior pole around the disc. No such feature was reported in the previous literature, even a few cases presented pigment proliferation in the macula [11–14]. Thirdly, the vision of the patient and her brother was not significantly impaired despite of the wide damages in the fundus.…”

Section: Discussionmentioning

confidence: 80%

“…To date, there were few reports of ML/DHRD. In China mainland, there was only one case report of R345W mutation in EFEMP1 caused ML/DHRD in a family [14]. In that report, 6 members of one family at the age of 37–61 yrs., and the proband was 43 yrs., all of whom showed drusen distributed in the fundus, 2 had RPE disorders and CNV.…”

Section: Discussionmentioning

confidence: 99%

Doyne honeycomb retinal dystrophy/malattia leventinese induced by EFEMP1 mutation in a Chinese family

et al. 2018

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BackgroundDoyne honeycomb retinal dystrophy (DHRD)/malattia leventinese (ML) is a rare allelic condition with massive drusen in the posterior fundus caused by EFEMP1 gene mutation. Patients showed decreased vision when the lesion affected the macular area. At present, the treatment efficiency is not satisfactory.Case presentationIn this study, we presented a family with DHRD/ML disease and analyzed the pathological and genetic information. A 28-year-old female patient presented to our department due to impaired visual acuity for 10 years especially in the right eye with deterioration for 5 months. Gene sequencing was performed by MyGenostics (Peking, China). Gene sequencing results revealed heterozygous mutations in EFEMP1 gene, which were consistent with the DHRD/ ML. Single heterozygous mutation (c.1033C > T) was observed in each of the three blood samples. This missense mutation triggered p.R345W.ConclusionsDHRD/ML is a rare disease associated with EFEMP1 gene mutation. Up to now, we are not sure whether these lesions are associated with the onset of DHRD/ML. In future, we hope to find out the exact relationship between them.

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“…La variante patogénica p.Arg345Trp, identificada en esta familia, es la única asociada con la enfermedad hasta el momento en diferentes poblaciones 1 , 5 - 8 . En los estudios en pacientes de diferentes etnias, solo una vez se logró determinar esta variante en un ancestro común de origen suizo 1 .…”

Section: Discussionunclassified

“…La malattia leventinese fue descrita por primera vez en individuos originarios del valle Leventina, en el sur de Suiza, de ahí su nombre 5 . Hasta el momento, solo se ha reportado una variante patogénica en el gen EFEMP1 como causante de la enfermedad, la c.1033C>T/p.Arg345Trp 1 , 6 , 7 , la cual se ha detectado en población sueca, británica, australiana, norteamericana, japonesa y coreana 8 .…”

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Definición diagnóstica en una familia con malattia leventinese en Colombia

Gélvez

Hurtado‐Villa

Flórez³

et al. 2021

biomedica

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La malattia leventinese es una enfermedad hereditaria autosómica dominante, cuyos síntomas se inician entre la segunda y la cuarta décadas de la vida. Se caracteriza por la aparición de drusas localizadas entre el epitelio pigmentario de la retina y la membrana de Bruch; suele reducir la visión drásticamente y progresar a ceguera. La variante patogénica p.Arg345Trp en el gen EFEMP1 se ha asociado con esta enfermedad.Se presenta aquí la caracterización clínica y molecular de una familia con malattia leventinese mediante un manejo integral que involucró a oftalmólogos, pediatras y genetistas, lo que es de gran importancia, ya que el fenotipo de esta enfermedad suele confundirse con la degeneración macular. A todos los individuos de la familia se les hizo la evaluación oftalmológica con imágenes diagnósticas de retina y extracción de ADN a partir de una muestra de sangre periférica. Todos los exones del gen EFEMP1 se amplificaron y secuenciaron. La variante patogénica p.Arg345Trp se identificó en los individuos afectados.Este es el primer reporte de malattia leventinese en una familia con la variante patogénica p.Arg345Trp en Colombia. El diagnóstico molecular de las distrofias retinianas es fundamental para diferenciar este tipo de enfermedades.

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Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy in a Chinese Family With Mutation of the Efemp1 Gene

Abstract: The R345W mutation in EFEMP1 caused Malattia leventinese/Doyne honeycomb retinal dystrophy in a Chinese family. This is the first report, as per our knowledge, of the R345W mutation in EFEMP1 in a Chinese pedigree of this disease.

Cited by 14 publications

References 23 publications

Exome Sequencing Identifies a Missense Variant in EFEMP1 Co-Segregating in a Family with Autosomal Dominant Primary Open-Angle Glaucoma

Exome Sequencing Identifies a Missense Variant in EFEMP1 Co-Segregating in a Family with Autosomal Dominant Primary Open-Angle Glaucoma

Doyne honeycomb retinal dystrophy/malattia leventinese induced by EFEMP1 mutation in a Chinese family

Definición diagnóstica en una familia con malattia leventinese en Colombia

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