Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His

Blevins, Gregg; Macaulay, Robert J.B.; Harder, Sheri; Fladeland, Derek; Yamashita, Taro; Yazaki, Masahide; Asl, Kamran Hamidi; Benson, Merrill D.; Donat, Jane F.

doi:10.1212/01.wnl.0000065901.18353.ab

Cited by 66 publications

(43 citation statements)

References 20 publications

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“…There may be some overlap with the FAP phenotype involving both central and peripheral nervous system [6]. Ten different TTR gene mutations (Leu12Pro, Asp18Gly, Ala25Thr, Val30Met, Val30Gly, Ala36Pro, Gly53Glu, Phe64Ser, Tyr69His, Tyr114Cys) associated with leptomeningeal amyloidosis have been reported [4][5][6][7][8][9][10][11][12][13]. Here we report a case of leptomeningeal amyloidosis with a novel point mutation at codon 49 of the TTR gene, leading to proline-for-threonine substitution.…”

Section: Introductionmentioning

confidence: 89%

A new Thr49Pro transthyretin gene mutation associated with leptomeningeal amyloidosis

Nakagawa

Sheikh

Snuderl

et al. 2008

Journal of the Neurological Sciences

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Section: Introductionmentioning

confidence: 89%

A new Thr49Pro transthyretin gene mutation associated with leptomeningeal amyloidosis

Nakagawa

Sheikh

Snuderl

et al. 2008

Journal of the Neurological Sciences

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“…There is some recognized phenotypic variability where the clinical characteristics within the hereditary group include a broader spectrum of presentations than within sporadic disease, usually with a younger age of onset (Table 1). Clinical signs in the hereditary forms can include spastic paraparesis, extrapyramidal signs, progressive ataxia or ocular disturbances, features that have not been part of the spectrum of sporadic cases [66][67][68][69][70][71][72][73][74][75].…”

Section: Hereditary Forms Of Caamentioning

confidence: 99%

Clinical phenotypes of Cerebral Amyloid Angiopathy

Maia¹,

Feldman

2007

Journal of the Neurological Sciences

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The term Cerebral Amyloid Angiopathy (CAA) is used to describe the pathological changes occurring in cerebral blood vessels, both leptomeningeal and cortical that result from the deposition of amyloid proteins. This CNS vasculopathy is associated with a spectrum of clinical phenotypes that include both ischemic and hemorrhagic presentations. Dementia, cognitive impairment and transient neurological symptoms or signs are also being increasingly recognized as part of the CAA clinical spectrum.This review covers the clinical, pathological and neuroimaging aspects of CAA.

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“…39 Vitreous opacities are much more common, seen with approximately 20% of transthyretin mutations, and may be the first manifestation of FAP. 46,75 Vitreous opacities may be a part of the oculoleptomeningeal syndrome of amyloid deposition, 10,23,70 or associated with amyloid cardiomyopathy without leptomeningeal involvement (Table 1). 19,57 Oculoleptomeningeal amyloidosis may be restricted to intracranial and spinal fibril deposition and presents with symptoms of stroke, seizures, hydrocephalus, spinal cord infarction or, later, cerebral hemorrhage.…”

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confidence: 99%

“…In leptomeningeal amyloidosis, deposits were seen in vascular and surrounding connective tissue structures. 10,23 This commonly leads to a clinical presentation with cerebral infarcts or, in later stages, cerebral hemorrhage. Infarcts may involve basal ganglia and the spinal cord.…”

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confidence: 99%

The molecular biology and clinical features of amyloid neuropathy

Benson¹,

Kincaid²

2007

Muscle and Nerve

398

312

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Neuropathy is often a major manifestation of systemic amyloidosis. It is most frequently seen in patients with hereditary transthyretin (TTR) amyloidosis, but is also present in 20% of patients with systemic immunoglobulin light chain (primary) amyloidosis. Familial amyloid polyneuropathy (FAP) is the most common form of inherited amyloidotic polyneuropathy, with clinical and electrophysiologic findings similar to neuropathies with differing etiologies (e.g., diabetes mellitus). Hereditary amyloidosis is an adult-onset autosomal-dominant disease with varying degrees of penetrance. It is caused by specific gene mutations, but demonstration that a patient has one such mutation does not confirm the diagnosis of amyloidosis. Diagnosis requires tissue biopsy with demonstration of amyloid deposits either by special histochemical stains or electron microscopy. Transthyretin amyloidosis is treated by liver transplantation, which eliminates the mutated transthyretin from the blood, but for some patients continued amyloid deposition can occur from wild-type (normal) transthyretin. Presently, a study is ongoing to determine whether amyloid deposition can be inhibited by small organic molecules that are hypothesized to affect the fibril-forming ability of transthyretin. Proposed gene therapy with antisense oligonucleotides (ASOs) to suppress hepatic transthyretin synthesis is effective in a transgenic mouse model but has not yet been tested in humans.

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Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His

Cited by 66 publications

References 20 publications

A new Thr49Pro transthyretin gene mutation associated with leptomeningeal amyloidosis

A new Thr49Pro transthyretin gene mutation associated with leptomeningeal amyloidosis

Clinical phenotypes of Cerebral Amyloid Angiopathy

The molecular biology and clinical features of amyloid neuropathy

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