Autosomal Dominant Frontotemporal Lobar Degeneration in a Filipino Family with Progranulin Mutation

2021 ◽  
pp. 1-8
Author(s):  
Jacqueline Dominguez ◽  
Arlene Ng ◽  
Jeryl Yu ◽  
Anne Cristine Guevarra ◽  
Maria Luisa Daroy ◽  
...  
Keyword(s):  
Frontotemporal Lobar Degeneration ◽  
White Matter Hyperintensities ◽  
Autosomal Dominant ◽  
The Philippines ◽  
Vascular Risk ◽  
Case Presentation ◽  
Nonfluent Aphasia ◽  
Protein Tau ◽  
Review Reports ◽  
Progressive Nonfluent Aphasia

<b><i>Background:</i></b> Compared to Western populations, familial frontotemporal lobar degeneration (FTLD) is rare among Asians. Progranulin (GRN) gene mutation, which is a major cause of FTLD, is likewise rare. We present a family with FTLD from the Philippines with an autosomal dominant pattern of inheritance and GRN mutation and briefly review reports of GRN mutations in Asia. <b><i>Case Presentation:</i></b> The proband is 66 years old with progressive nonfluent aphasia (PNFA)-corticobasal syndrome . We assessed 3 generations of her pedigree and found 11 affected relatives with heterogenous phenotypes, usually behavioral variant frontotemporal dementia (FTD) and PNFA. Neuroimaging showed atrophy and hypometabolism consistent with FTD syndromes. White matter hyperintensities were seen in affected members even in the absence of vascular risk factors. A GRN mutation R110X was found in 6 members, 3 with symptoms and 3 were asymptomatic. Plasma GRN was low (&#x3c;112 ng/mL) in all mutation carriers. No mutations were found in microtubule-associated protein tau, APP, PSEN1, and PSEN2 genes, and all were APOE3. <b><i>Conclusion:</i></b> This is the first Filipino family with autosomal dominant FTD documented with GRN mutation. Identifying families and cohorts would contribute to therapeutic developments in an area with FTD-GRN.

Frontotemporal Lobar Degeneration: Characterizing Semantic Binding and Abstracted Meaning Abilities

2009 ◽  
Vol 19 (4) ◽  
pp. 117-125 ◽  
Author(s):  
Raksha Anand ◽  
John Hart ◽  
Patricia S. Moore ◽  
Sandra B. Chapman
Keyword(s):  
Frontotemporal Lobar Degeneration ◽  
Assessment Tools ◽  
Progressive Decline ◽  
Cognitively Normal ◽  
Nonfluent Aphasia ◽  
Traditional Assessment ◽  
Language Measures ◽  
Semantic Object ◽  
Semantic Problem ◽  
Progressive Nonfluent Aphasia

Abstract Purpose: Frontotemporal lobar degeneration (FTLD) encompasses a group of neurodegenerative disorders characterized by gradual and progressive decline in behavior and/or language. Identifying the subtypes of FTLD can be challenging with traditional assessment tools. Growing empirical evidence suggests that language measures might be useful in differentiating FTLD subtypes. Method: In this paper, we examined the performance of five individuals with FTLD (two with frontotemporal dementia, two with semantic dementia, and one with progressive nonfluent aphasia) and 10 cognitively normal older adults on measures of semantic binding (Semantic Object Retrieval Test and semantic problem solving) and abstracted meaning (generation of interpretive statement and proverb interpretation). Results and Conclusion: A differential profile of impairment was observed in the three FTLD subtypes on these four measures. Further examination of these measures in larger groups will establish their clinical utility in differentiating the FTLD subtypes.

Current Concepts in the Classification and Diagnosis of Frontotemporal Lobar Degenerations: A Practical Approach

2014 ◽  
Vol 138 (1) ◽  
pp. 132-138 ◽  
Author(s):  
Zdenek Rohan ◽  
Radoslav Matej
Keyword(s):  
Frontotemporal Dementia ◽  
Glial Cells ◽  
Tau Protein ◽  
Frontotemporal Lobar Degeneration ◽  
Dna Binding Protein ◽  
Nonfluent Aphasia ◽  
Fused In Sarcoma ◽  
Clinical Syndromes ◽  
Pathologic Processes ◽  
Progressive Nonfluent Aphasia

Frontotemporal lobar degenerations are clinically, genetically, and molecularly heterogeneous diseases characterized by mainly frontal and temporal atrophy and affecting behavioral, language, cognitive, and motor functions. The term frontotemporal dementia incorporates 3 distinct clinical syndromes seen in frontotemporal degenerations: behavioral variant of frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia. Progressive supranuclear palsy syndrome, corticobasal syndrome, and motor neuron disease syndrome are also associated with frontotemporal lobar degenerations. The neuropathologic hallmark of frontotemporal lobar degenerations is accumulation of abnormal proteins in the cytoplasm and nuclei of neurons and glial cells. Proteins involved in pathologic processes that represent the basis for frontotemporal lobar degeneration classification are tau protein, transactive response DNA-binding protein of 43 kDa, and “fused in sarcoma” protein. The aim of this review is to provide a summary of practical approaches for neuropathologic diagnostics of the rapidly evolving classifications of frontotemporal lobar degenerations.

Efficacy and safety of denosumab treatment in a prepubertal patient with cherubism

2020 ◽  
Vol 33 (7) ◽  
pp. 963-966
Author(s):  
Haruka Kawamura ◽  
Satoshi Watanabe ◽  
Takashi I ◽  
Izumi Asahina ◽  
Hiroyuki Moriuchi ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Therapeutic Potential ◽  
Giant Cells ◽  
Efficacy And Safety ◽  
Autosomal Dominant Disorder ◽  
Osteolytic Lesions ◽  
Case Presentation ◽  
Childhood Growth ◽  
Receptor Activator ◽  
Denosumab Treatment

AbstractBackgroundDenosumab is an inhibitor of receptor activator of nuclear factor kappa-B ligand, which strongly suppresses osteoclasts. Cherubism is a rare autosomal dominant disorder characterized by symmetrical swelling of the jaws, in which the bone is replaced by a fibrous granuloma containing osteoclast-like giant cells.Case presentationWe report the efficacy and safety of denosumab treatment in a prepubertal boy with progressive cherubism. The treatment consisting of eight subcutaneous denosumab injections (120 mg/dose) in 6 months not only suppressed the expansion of the osteolytic lesions but also dramatically ossified them. However, a transiently decreased growth rate and rebounded asymptomatic hypercalcemia were associated with the treatment.ConclusionsThe present case demonstrated the therapeutic potential of denosumab for treatment of cherubism, although adverse effects, especially those on childhood growth, remain obscure. Further studies are needed to establish a safe and effective protocol for denosumab treatment of children.

scholarly journals The Genetics of Monogenic Frontotemporal Dementia

2015 ◽  
Vol 9 (3) ◽  
pp. 219-229 ◽  
Author(s):  
Leonel T. Takada
Keyword(s):  
Frontotemporal Dementia ◽  
Autosomal Dominant ◽  
Positive Family History ◽  
Chromosome 9 ◽  
Complex Phenotype ◽  
Reading Frame ◽  
Protein Tau ◽  
Paget Disease ◽  
Fused In Sarcoma ◽  
Spectrum Disorders

ABSTRACT Around 10-15% of patients diagnosed with frontotemporal dementia (FTD) have a positive family history for FTD with an autosomal dominant pattern of inheritance. Since the identification of mutations in MAPT(microtubuleassociated protein tau gene) in 1998, over 10 other genes have been associated with FTD spectrum disorders, discussed in this review. Along with MAPT, mutations in GRN(progranulin) and C9orf72(chromosome 9 open reading frame 72) are the most commonly identified in FTD cohorts. The association of FTD and motor neuron disease (MND) can be caused by mutations in C9orf72and other genes, such as TARDBP(TAR DNA-binding protein), FUS(fused in sarcoma), UBQLN2(ubiquilin 2). Multisystem proteinopathy is a complex phenotype that includes FTD, Paget disease of the bone, inclusion body myopathy and MND, and can be due to mutations in VCP(valosing containing protein) and other recently identified genes.

scholarly journals Copy number variation in MODY diabetes - Familial case presentation

2018 ◽  
Vol 2 (2) ◽  
pp. 73
Author(s):  
Naida Lojo-Kadric ◽  
Zelija Velija Asimi ◽  
Jasmin Ramic ◽  
Ksenija Radic ◽  
Lejla Pojskic
Keyword(s):  
Insulin Secretion ◽  
Copy Number ◽  
Autosomal Dominant ◽  
Single Gene ◽  
Maturity Onset Diabetes ◽  
Dominant Form ◽  
Case Presentation ◽  
Monogenic Diseases ◽  
Number Variation ◽  
Autosomal Dominant Form

MODY (maturity-onset diabetes of the young) is an autosomal dominant form of diabetes that is usually manifested before the 25-year of life. This type of diabetes is caused by defects in the primary insulin secretion. There are several types of MODY, which are monogenic diseases, where mutations in a single gene are responsible for a particular type of MODY. Currently, there are eleven types of MODY, from which the most common types are MODY 2 and MODY 3 (with mutations on GCK and HNF1A genes, respectively). We identified very rare MODY 7 type of diabetes in three family members by MLPA analysis.

scholarly journals Prenatal Diagnosis of Holt–Oram Syndrome With a Novel Mutation of TBX5 Gene: A Case Report

2021 ◽  
Vol 9 ◽  
Author(s):  
Guan-nan He ◽  
Xue-yan Wang ◽  
Min Kang ◽  
Xi-min Chen ◽  
Na Xi ◽  
...  
Keyword(s):  
Septal Defect ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Splice Donor ◽  
Autosomal Dominant Disorder ◽  
Cubitus Valgus ◽  
Case Presentation ◽  
Whole Exome ◽  
The Right ◽  
Tbx5 Gene

Background: Holt–Oram syndrome (HOS) is an autosomal dominant disorder caused by mutations of TBX5 gene.Case presentation: We report a fetus with HOS diagnosed sonographically at 23 weeks of gestation. The fetal parents are non-consanguineous. The fetus exhibited short radius and ulna, inability to supinate the hands, absence of the right thumb, and heart ventricular septal defect (VSD), while the fetal father exhibited VSD and short radius and ulna only. Fetal brother had cubitus valgus and thumb adduction, except for VSD, short radius and ulna. The pregnancy was terminated. Whole-exome sequencing (WES) revealed a novel mutation in the TBX5 (c.510+1G&gt;A) in the fetus inherited from the father. The variant (c.510+1G&gt;A) occurs at splice donor and may alter TBX5 gene function by impact on splicing. It was not previously reported in China.Conclusion: Our case reported a novel mutation in TBX5, which expanded the known genetic variants associated with HOS.

P4-074: ITALIAN NETWORK FOR AUTOSOMAL DOMINANT ALZHEIMER'S DISEASE AND FRONTOTEMPORAL LOBAR DEGENERATION (ITALIANDIAFN)

2014 ◽  
Vol 10 ◽  
pp. P810-P810
Author(s):  
Martina Bocchetta ◽  
Michela Pievani ◽  
Claudio Babiloni ◽  
Amalia C. Bruni ◽  
Elio Scarpini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Lobar Degeneration ◽  
Autosomal Dominant ◽  
Autosomal Dominant Alzheimer’S Disease

Providing Augmentative and Alternative Communication Treatment to Persons With Progressive Nonfluent Aphasia

2010 ◽  
Vol 20 (1) ◽  
pp. 21-25 ◽  
Author(s):  
Melanie Fried-Oken ◽  
Charity Rowland ◽  
Chris Gibbons
Keyword(s):  
Augmentative And Alternative Communication ◽  
Clinical Implications ◽  
Disease Course ◽  
Alternative Communication ◽  
Future Directions ◽  
Verbal Expression ◽  
Nonfluent Aphasia ◽  
Oregon Health ◽  
And Training ◽  
Progressive Nonfluent Aphasia

Abstract Augmentative and alternative communication (AAC) intervention offers people diagnosed with progressive nonfluent aphasia (PNFA) an opportunity to continue to communicate even as verbal expression declines. To date, there are no well-controlled studies reporting the effectiveness of AAC intervention with people who present with PNFA. Further, there is a pressing need for evidence about specific AAC intervention tools, techniques, and training protocols for persons with PNFA and their communication partners. We have engaged in research studies at the Oregon Health & Science University to quantify low-tech AAC supports for people with PNFA in highly controlled, as well as naturalistic, dyadic conversations. Preliminary results suggest that AAC provides strong lexical support for people with PNFA during conversation. We predict that training participants and their partners how to use personalized, low-tech communication boards will lead to reduced conversational scaffolding by partners and prolonged effective communication as the disease course progresses. Clinical implications and future directions of our research are discussed.

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