Ocular Abnormalities in Mucolipidosis Iv

Riedel, K. G.; Zwaan, Johan; Kenyon, Kenneth R.; Kolodny, Edwin H.; Hanninen, Laila A.; Albert, David E.

doi:10.1016/0002-9394(85)90220-x

Cited by 62 publications

(33 citation statements)

References 13 publications

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“…Symptoms appear during the first year of life and include intellectual disabilities, psychomotor delay, weak muscle tone (hypotonia), corneal clouding and progressive retinal degeneration (Berman et al, 1974;Riedel et al, 1985). In addition, MLIV patients show impaired secretion of gastric acid (achlorhydria) leading to defective iron absorption and anemia (Schiffmann et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

LAPTMs regulate lysosomal function and interact with mucolipin 1: new clues for understanding mucolipidosis type IV

Vergarajaúregui

Martina

Puertollano

2011

Journal of Cell Science

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SummaryLoss-of-function mutations in mucolipin 1 (MCOLN1) result in mucolipidosis type IV (MLIV), a lysosomal storage disorder characterized by severe mental and psychomotor retardation. MCOLN1 is a lysosomal ion channel that belongs to the transient receptor potential (TRP) superfamily. To better understand the cellular function of MCOLN1, a split-ubiquitin yeast two-hybrid screen was performed with the purpose of revealing new MCOLN1 interaction partners. The screen identified two members of the lysosomeassociated protein transmembrane (LAPTM) family as novel interaction partners of MCOLN1. The binding between MCOLN1 and LAPTM members (LAPTMs) was confirmed by co-immunoprecipitation and yeast two-hybrid assays. In addition, MCOLN1 and LAPTMs extensively colocalize at late endosomes and lysosomes. Overexpression of LAPTM4b caused enlargement of lysosomes and defective lysosomal degradation, indicating that LAPTMs are important for proper lysosomal function. Interestingly, lysosomal swelling induced by LAPTM4b was rescued by expression of MCOLN1, suggesting a functional connection between the two proteins. Finally, depletion of endogenous LAPTMs by siRNA induced accumulation of concentric multi-lamellar structures and electron-dense inclusions that closely resemble the structures found in MLIV cells. Overall, our data provide new insight into the molecular mechanisms of MCOLN1 function and suggest a potential role for LAPTMs in MLIV pathogenesis.

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Section: Introductionmentioning

confidence: 99%

LAPTMs regulate lysosomal function and interact with mucolipin 1: new clues for understanding mucolipidosis type IV

Vergarajaúregui

Martina

Puertollano

2011

Journal of Cell Science

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“…This was proven histologically in an advanced ML IV case in which optic nerve and receptor atrophy with intraretinal pig ment epithelial cells and pigment-laden ma crophages migration was found [10].…”

Section: Discussionmentioning

confidence: 97%

“…3, 7] and optic nerve conduction defect [2. 7], These elcctrophysiological changes and the atrophic alterations recently docu mented histologically in an advanced case of ML IV [10] seem to hint to a possible retinal pathological similarity in ML IV and tapetoretinal dystrophy. In the present stu dy, the visual function in ML IV was exam ined by ERG and VEP recordings in a young patient at 9 years interval, and the progressive elcctrophysiological alterations compared with those occurring in cases of tapetoretinal dystrophy.…”

mentioning

confidence: 99%

Retinal Function in Mucolipidosis IV

et al. 1985

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In an 18-month-old girl affected by mucolipidosis IV (ML IV) with mild corneal clouding, normal retinal activity was documented by electroretinogram (ERG) and slightly delayed optic pathway conduction was revealed by visual evoked potential (VEP). Re-examination 9 years later disclosed severe retinal alterations resulting in atrophy with reduced photopic and missing scotopic ERG components and flat VEP. These fundoscopic and electrophysiologic deteriorations in ML IV suggest progressive rod-cone impairment similar to tapetoretinal dystrophy.

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“…The corneal clouding, when present, is usually mild. Hyperopic astigmatism, pigmentary retinopathy, surface-wrinkling maculopathy, retinal vascular tortuosity, optic nerve head swelling, and severe optic atrophy have been also reported with this disease [33,34].…”

Section: Mucolipidosesmentioning

confidence: 93%

“…In some of the mucolipidoses, ocular manifestations are common and may include corneal clouding, macular grayness, or a cherry red spot [33]. The corneal clouding, when present, is usually mild.…”

Section: Mucolipidosesmentioning

confidence: 98%