Mutations in Progranulin Gene: Clinical, Pathological, and Ribonucleic Acid Expression Findings

Munáin, Adolfo López de; Alzualde, Ainhoa; Gorostidi, Ana; Otaegui, David; Ruíz‐Martínez, Javier; Indakoetxea, Begoña; Ferrer, Isidro; Pérez-Tur, Jordi; Sáenz, Amets; Bergareche, Alberto; Barandiarán, Miriam; Poza, Juan José; Zabalza, R; Ruiz, Irune; Urtasun, Miguel; Fernández-Manchola, I; Olasagasti, Bixen; Espinal, Juan Bautista; Olaskoaga, J; Ruibal, M.; Moreno, Fermín; Carrera, N; Massó, Jose Félix Martí

doi:10.1016/j.biopsych.2007.08.015

Cited by 62 publications

(46 citation statements)

References 42 publications

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“…Familial CBS may be associated with granulin (GRN) mutations and frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions (FTLD-TDP) (i.e., nontau) pathology rather than with CBD. [54][55][56] Comparison of phenotypes. Studies comparing the different CBD phenotypes are described in the supplemental text.…”

Section: Resultsmentioning

confidence: 99%

Criteria for the diagnosis of corticobasal degeneration

et al. 2013

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Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset $50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype.Future validation and refinement of the proposed criteria are needed. When first described, "corticodentatonigral degeneration with neuronal achromasia" was considered a distinct clinicopathologic entity, 1 eventually termed corticobasal degeneration (CBD). 2Clinicopathologic studies have since revealed that the originally described clinical features of CBD, now called corticobasal syndrome (CBS), are often due to other pathologies. As a pathologic diagnosis, CBD is characterized by widespread deposition of hyperphosphorylated 4-repeat tau in neurons and glia, the latter as astrocytic plaques, in specific topographic areas. 3 Despite various clinical diagnostic criteria (table e-1 on the Neurology ® Web site at www.neurology.org), 4-10 the pathology of CBD is predicted antemortem in only 25% to 56% of cases.11-17 Additionally, while these clinical criteria continue to be widely applied and cited, they reflect CBS alone and not the more recently recognized behavioral presentations of CBD.

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Section: Resultsmentioning

confidence: 99%

Criteria for the diagnosis of corticobasal degeneration

et al. 2013

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“…In addition, mild parkinsonian features are frequent but motor neuron disease was remarkably rare Josephs et al, 2007;Mackenzie, 2007]. Furthermore, other neurodegenerative brain diseases including corticobasal syndrome (CBS) [Masellis et al, 2006;Benussi et al, 2008;Rademakers et al, 2007;Le Ber et al, 2007;Lopez de Munain et al, 2008;Spina et al, 2007b;Le Ber et al, 2008], AD [van Duijn et al, 1994;Rademakers et al, 2002;Brouwers et al, 2007;Rademakers et al, 2007] and PD [Brouwers et al, 2007] were also linked with GRN mutations. However, compared to variants with unclear pathogenic significance, GRN null mutations were not frequently found in patients with a disease other than FTLD Schymick et al, 2007;Brouwers et al, 2007;Sleegers et al, in press;Pickering-Brown et al, 2008].…”

Section: Clinical Biological and Diagnostic Significance Genotype-pmentioning

confidence: 99%

Granulin mutations associated with frontotemporal lobar degeneration and related disorders: An update

2008

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Communicated by Mark H. PaalmanMutations in the gene encoding granulin (HUGO gene symbol GRN, also referred to as progranulin, PGRN), located at chromosome 17q21, were recently linked to tau-negative ubiquitin-positive frontotemporal lobar degeneration (FTLDU). Since then, 63 heterozygous mutations were identified in 163 families worldwide, all leading to loss of functional GRN, implicating a haploinsufficiency mechanism. Together, these mutations explained 5 to 10% of FTLD. The high mutation frequency, however, might still be an underestimation because not all patient samples were examined for all types of loss-of-function mutations and because several variants, including missense mutations, have a yet uncertain pathogenic significance. Although the complete phenotypic spectrum associated with GRN mutations is not yet fully characterized, it was shown that it is highly heterogeneous, suggesting the influence of modifying factors. A role of GRN in neuronal survival was suggested but the exact mechanism by which neurodegeneration and deposition of pathologic brain inclusions occur still has to be clarified. Hum Mutat 29(12), [1373][1374][1375][1376][1377][1378][1379][1380][1381][1382][1383][1384][1385][1386] 2008.

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“…Patients from different families with the same mutation do not necessarily show the same clinical phenotype or age at onset (Huey, Grafman et al 2006). On microscopic examination, all cases with PGRN mutations share a common subtype, characterized by NCIs and irregular dystrophic neurites in the neocortex and subcortical nuclei (Josephs, Ahmed et al 2007;Gass, Cannon et al 2006;Behrens, Mukherjee et al 2007;Lopez de Munain, Alzualde et al 2008;Mackenzie, Baker et al 2006;Snowden, PickeringBrown et al 2006;Spina, Murrell et al 2007). This subtype is referred to as type A (Mackenzie, Neumann et al).…”

Section: Pgrnmentioning

confidence: 99%

Frontotemporal Lobar Degeneration

Kanekar¹

2016

Imaging of Neurodegenerative Disorders

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Mutations in Progranulin Gene: Clinical, Pathological, and Ribonucleic Acid Expression Findings

Cited by 62 publications

References 42 publications

Criteria for the diagnosis of corticobasal degeneration

Criteria for the diagnosis of corticobasal degeneration

Granulin mutations associated with frontotemporal lobar degeneration and related disorders: An update

Frontotemporal Lobar Degeneration

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