Abstract
Genetics is intricately involved in the etiology of neurodegenerative dementias. The incidence of monogenic dementia among all neurodegenerative forms is unknown due to the lack of systematic studies and of patient/clinician access to extensive diagnostic procedures. In this study, we conducted targeted sequencing in 246 clinically heterogeneous patients, mainly with early-onset and/or familial neurodegenerative dementia, using a custom-designed next-generation sequencing panel covering 27 genes known to harbor mutations that can cause different types of dementia, in addition to the detection of C9orf72 repeat expansions. Forty-nine patients (19.9%) carried known pathogenic or novel, likely pathogenic, variants, involving both common (presenilin 1, presenilin 2, C9orf72, and granulin) and rare (optineurin, serpin family I member 1 and protein kinase cyclic adenosine monophosphate (cAMP)-dependent type I regulatory subunit beta) dementia-associated genes. Our results support the use of an extended next-generation sequencing panels as a quick, accurate, and cost-effective method for diagnosis in clinical practice. This approach could have a significant impact on the proportion of tested patients, especially among those with an early disease onset.
| Original language | English |
|---|---|
| Pages (from-to) | 180.e23-180.e31 |
| Journal | Neurobiology of Aging |
| Volume | 66 |
| DOIs | |
| Publication status | Published - Jun 1 2018 |
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Keywords
- C9orf72 RE
- Double mutations
- Familial dementia
- Neurodegenerative dementia
- Next-generation sequencing
- Targeted gene sequencing
ASJC Scopus subject areas
- Neuroscience(all)
- Ageing
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology
Cite this
Identification of rare genetic variants in Italian patients with dementia by targeted gene sequencing. / Bartoletti-Stella, Anna; Baiardi, Simone; Stanzani-Maserati, Michelangelo; Piras, Silvia; Caffarra, Paolo; Raggi, Alberto; Pantieri, Roberta; Baldassari, Sara; Caporali, Leonardo; Abu-Rumeileh, Samir; Linarello, Simona; Liguori, Rocco; Parchi, Piero; Capellari, Sabina.
In: Neurobiology of Aging, Vol. 66, 01.06.2018, p. 180.e23-180.e31.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identification of rare genetic variants in Italian patients with dementia by targeted gene sequencing
AU - Bartoletti-Stella, Anna
AU - Baiardi, Simone
AU - Stanzani-Maserati, Michelangelo
AU - Piras, Silvia
AU - Caffarra, Paolo
AU - Raggi, Alberto
AU - Pantieri, Roberta
AU - Baldassari, Sara
AU - Caporali, Leonardo
AU - Abu-Rumeileh, Samir
AU - Linarello, Simona
AU - Liguori, Rocco
AU - Parchi, Piero
AU - Capellari, Sabina
N1 - "Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Liguori Rocco, Parchi Piero, Capellari Sabina)
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Genetics is intricately involved in the etiology of neurodegenerative dementias. The incidence of monogenic dementia among all neurodegenerative forms is unknown due to the lack of systematic studies and of patient/clinician access to extensive diagnostic procedures. In this study, we conducted targeted sequencing in 246 clinically heterogeneous patients, mainly with early-onset and/or familial neurodegenerative dementia, using a custom-designed next-generation sequencing panel covering 27 genes known to harbor mutations that can cause different types of dementia, in addition to the detection of C9orf72 repeat expansions. Forty-nine patients (19.9%) carried known pathogenic or novel, likely pathogenic, variants, involving both common (presenilin 1, presenilin 2, C9orf72, and granulin) and rare (optineurin, serpin family I member 1 and protein kinase cyclic adenosine monophosphate (cAMP)-dependent type I regulatory subunit beta) dementia-associated genes. Our results support the use of an extended next-generation sequencing panels as a quick, accurate, and cost-effective method for diagnosis in clinical practice. This approach could have a significant impact on the proportion of tested patients, especially among those with an early disease onset.
AB - Genetics is intricately involved in the etiology of neurodegenerative dementias. The incidence of monogenic dementia among all neurodegenerative forms is unknown due to the lack of systematic studies and of patient/clinician access to extensive diagnostic procedures. In this study, we conducted targeted sequencing in 246 clinically heterogeneous patients, mainly with early-onset and/or familial neurodegenerative dementia, using a custom-designed next-generation sequencing panel covering 27 genes known to harbor mutations that can cause different types of dementia, in addition to the detection of C9orf72 repeat expansions. Forty-nine patients (19.9%) carried known pathogenic or novel, likely pathogenic, variants, involving both common (presenilin 1, presenilin 2, C9orf72, and granulin) and rare (optineurin, serpin family I member 1 and protein kinase cyclic adenosine monophosphate (cAMP)-dependent type I regulatory subunit beta) dementia-associated genes. Our results support the use of an extended next-generation sequencing panels as a quick, accurate, and cost-effective method for diagnosis in clinical practice. This approach could have a significant impact on the proportion of tested patients, especially among those with an early disease onset.
KW - C9orf72 RE
KW - Double mutations
KW - Familial dementia
KW - Neurodegenerative dementia
KW - Next-generation sequencing
KW - Targeted gene sequencing
UR - http://www.scopus.com/inward/record.url?scp=85042934377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042934377&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2018.02.006
DO - 10.1016/j.neurobiolaging.2018.02.006
M3 - Article
C2 - 29525180
AN - SCOPUS:85042934377
VL - 66
SP - 180.e23-180.e31
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -