The Utility of Next-Generation Sequencing for Identifying the Genetic Basis of Dementia

The clinical manifestations of dementia are often rapidly matched to a specific clinical syndrome, but the underlying neuropathology is not always obvious. A genetic factor often plays an important role in early onset dementia, but there are cases in which the phenotype has a different genetic basis than is assumed. Two patients, at different times, presented to the Memory Clinic because of memory problems and difficulty in performing daily activities and work. Neither caregiver complained of marked behavioural or personality changes, except for apathy. Patients underwent standard dementia evaluation procedures including clinical symptoms, family history, neuroimaging, neuropsychological evaluation, and genetic analysis of selected genes. Based on specific clinical phenotypes and genetic analysis of selected genes, both patients were diagnosed with frontal variant of Alzheimer’s disease. The presence of a rare polymorphism in PSEN2 in both patients allowed the discovery that they belong to the same family. This fact reinforced the belief that there is a strong genetic factor responsible for causing dementia in the family. Next-generation sequencing based on a panel of 118 genes was performed to identify other potential genetic factors that may determine the background of the disease. A mutation in the GRN gene was identified, and the previous diagnosis was changed to frontotemporal dementia. The described cases show how important it is to combine all diagnostic tests available in the diagnostic centre, including new generation genetic tests, in order to establish/confirm the pathological background of clinical symptoms of dementia. If there is any doubt about the final diagnosis, persistent efforts should be made to verify the cause.

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Genetic Analysis of Chinese Patients with Early-Onset Dementia Using Next-Generation Sequencing

Clinical Interventions in Aging ◽

10.2147/cia.s271222 ◽

2020 ◽

Vol Volume 15 ◽

pp. 1831-1839

Author(s):

Li-Hong Han ◽

Yan-Yan Xue ◽

Yi-Cen Zheng ◽

Xiao-Yan Li ◽

Rong-Rong Lin ◽

...

Keyword(s):

Next Generation Sequencing ◽

Genetic Analysis ◽

Early Onset ◽

Chinese Patients ◽

Next Generation ◽

Early Onset Dementia ◽

Generation Sequencing

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Potential relationship between clinical symptoms and the root canal microbiomes of root filled teeth based on the next‐generation sequencing

International Endodontic Journal ◽

10.1111/iej.13640 ◽

2021 ◽

Author(s):

Yajing Hou ◽

Liu Wang ◽

Lan Zhang ◽

Xuelian Tan ◽

Dingming Huang ◽

...

Keyword(s):

Next Generation Sequencing ◽

Root Canal ◽

Clinical Symptoms ◽

Next Generation ◽

Potential Relationship ◽

Generation Sequencing

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A teljesexom-szekvenálás jelentősége a ritka neurológiai betegségek diagnosztikájában – saját tapasztalatok egy ataxiás eset kapcsán

Orvosi Hetilap ◽

10.1556/650.2018.31049 ◽

2018 ◽

Vol 159 (28) ◽

pp. 1163-1169 ◽

Cited By ~ 1

Author(s):

Péter Balicza ◽

Zoltán Grosz ◽

Renáta Bencsik ◽

Anett Illés ◽

Anikó Gál ◽

...

Keyword(s):

Next Generation Sequencing ◽

Exome Sequencing ◽

Cerebellar Ataxia ◽

Clinical Symptoms ◽

Spastic Paraparesis ◽

Gene Panel ◽

Next Generation ◽

Hereditary Spastic Paraparesis ◽

Disease Stratification ◽

Generation Sequencing

Abstract: Next generation sequencing (NGS) technologies reshape the diagnostics of rare neurological diseases. In the background of certain neurological symptoms, such as ataxia, many acquired and genetic causes may be present. Variations in a given gene can present with variable phenotypes, too. Because of this phenomenon, the conventional one gene sequencing approach often fails to identify the genetic background of a disease. Next generation sequencing panels allow to sequence 50–100 genes simultaneously, and if the disease stratification is not possible based on the clinical symptoms, whole exome sequencing can help in the diagnostic of genetic disorders with atypical presentation. This case study is about the exome sequencing of a patient with cerebellar ataxia. Genetic investigations identified rare variants in the SPG11 gene in association with the clinical phenotype, which gene was originally described in the background of hereditary spastic paraparesis. Our article highlights that in certain cases the variability of the leading presenting symptom makes it hard to select the correct gene panel. In our case the variants in the gene, formerly associated to hereditary spastic paraparesis, resulted in cerebellar ataxia initially, so even an ataxia NGS gene panel would not detect those. Orv Hetil. 2018; 159(28): 1163–1169.

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Detection of Listeria monocytogenes in a patient with meningoencephalitis using next-generation sequencing: a case report

BMC Infectious Diseases ◽

10.1186/s12879-020-05447-z ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Zi-Wei Lan ◽

Min-Jia Xiao ◽

Yuan-lin Guan ◽

Ya-Jing Zhan ◽

Xiang-Qi Tang

Keyword(s):

Listeria Monocytogenes ◽

Next Generation Sequencing ◽

Mammalian Cells ◽

Clinical Manifestations ◽

Bacterial Pathogen ◽

Next Generation ◽

Accurate Treatment ◽

The Central Nervous System ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

Abstract Background Listeria monocytogenes (L. monocytogenes) is a facultative intracellular bacterial pathogen which can invade different mammalian cells and reach to the central nervous system (CNS), leading to meningoencephalitis and brain abscesses. In the diagnosis of L. monocytogenes meningoencephalitis (LMM), the traditional test often reports negative owing to the antibiotic treatment or a low number of bacteria in the cerebrospinal fluid. To date, timely diagnosis and accurate treatment remains a challenge for patients with listeria infections. Case presentation We present the case of a 66-year-old woman whose clinical manifestations were suspected as tuberculous meningoencephalitis, but the case was finally properly diagnosed as LMM by next-generation sequencing (NGS). The patient was successfully treated using a combined antibacterial therapy, comprising ampicillin and trimethoprim-sulfamethoxazole. Conclusion To improve the sensitivity of LMM diagnosis, we used NGS for the detection of L. monocytogenes. Hence, the clinical utility of this approach can be very helpful since it provides quickly and trust results.

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Balamuthia mandrillaris-Related Primary Amoebic Encephalitis in China Diagnosed by Next Generation Sequencing and a Review of the Literature

Laboratory Medicine ◽

10.1093/labmed/lmz079 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yinan Yang ◽

Xiaobin Hu ◽

Li Min ◽

Xiangyu Dong ◽

Yuanlin Guan

Keyword(s):

Next Generation Sequencing ◽

Inflammatory Diseases ◽

Clinical Manifestations ◽

Infectious Agent ◽

Disease Diagnosis ◽

Rapid Identification ◽

Next Generation ◽

Balamuthia Mandrillaris ◽

Granulomatous Amoebic Encephalitis ◽

Generation Sequencing

Abstract Background Encephalitis is caused by infection, immune mediated diseases, or primary inflammatory diseases. Of all the causative infectious pathogens, 90% are viruses or bacteria. Granulomatous amoebic encephalitis (GAE), caused by Balamuthia mandrillaris, is a rare but life-threatening disease. Diagnosis and therapy are frequently delayed due to the lack of specific clinical manifestations. Method A healthy 2 year old Chinese male patient initially presented with a nearly 2 month history of irregular fever. We present this case of granulomatous amoebic encephalitis caused by B. mandrillaris. Next generation sequencing of the patient’s cerebrospinal fluid (CSF) was performed to identify an infectious agent. Result The results of next generation sequencing of the CSF showed that most of the mapped reads belonged to Balamuthia mandrillaris. Conclusion Next generation sequencing (NGS) is an unbiased and rapid diagnostic tool. The NGS method can be used for the rapid identification of causative pathogens. The NGS method should be widely applied in clinical practice and help clinicians provide direction for the diagnosis of diseases, especially for rare and difficult cases.

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The development of 10 novel polymorphic microsatellite markers through next generation sequencing and a preliminary population genetic analysis for the endangered Glenelg spiny crayfish, Euastacus bispinosus

Molecular Biology Reports ◽

10.1007/s11033-013-2531-5 ◽

2013 ◽

Vol 40 (7) ◽

pp. 4415-4419 ◽

Cited By ~ 10

Author(s):

Adam D. Miller ◽

Anthony Van Rooyen ◽

Oisín F. Sweeney ◽

Nick S. Whiterod ◽

Andrew R. Weeks

Keyword(s):

Next Generation Sequencing ◽

Genetic Analysis ◽

Microsatellite Markers ◽

Population Genetic ◽

Next Generation ◽

Population Genetic Analysis ◽

Polymorphic Microsatellite ◽

Generation Sequencing

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Melanoma Mimicking Malignant Peripheral Nerve Sheath Tumor with Spread to the Cerebellopontine Angle: Utility of Next-Generation Sequencing in Diagnosis

Case Reports in Pathology ◽

10.1155/2018/9410465 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Katie Fox Hanson ◽

Paul Birinyi ◽

Ronald Walker ◽

Constantine Raptis ◽

Rebecca Chernock ◽

...

Keyword(s):

Next Generation Sequencing ◽

Clinical Symptoms ◽

Cranial Nerves ◽

Melanocytic Lesion ◽

Nerve Sheath Tumor ◽

Next Generation ◽

Parotid Region ◽

Lentigo Maligna Melanoma ◽

Clinically Significant ◽

Generation Sequencing

Cutaneous spindle cell malignancy is associated with a broad differential diagnosis, particularly in the absence of a known primary melanocytic lesion. We present an unusually challenging patient who presented with clinical symptoms involving cranial nerves VII and VIII and a parotid-region mass, which was S100-positive while lacking in melanocytic pigment and markers. Over a year after resection of the parotid mass, both a cutaneous primary lentigo maligna melanoma and a metastatic CP angle melanoma were diagnosed in the same patient, prompting reconsideration of the diagnosis in the original parotid-region mass. Next-generation sequencing of a panel of cancer-associated genes demonstrated 19 identical, clinically significant mutations as well as a high tumor mutation burden in both the parotid-region and CP angle tumors, indicating a metastatic relationship between the two and a melanocytic identity of the parotid-region tumor.

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