Abstract
Original language | English |
---|---|
Pages (from-to) | 2017-2023 |
Number of pages | 7 |
Journal | American journal of human genetics |
Volume | 108 |
Issue number | 10 |
DOIs | |
Publication status | Published - 7 Oct 2021 |
Keywords
- ABHD16A
- hereditary spastic paraplegia
- intellectual disability
- lysophosphatidylserine
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In: American journal of human genetics, Vol. 108, No. 10, 07.10.2021, p. 2017-2023.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia associated with intellectual disability and cerebral anomalies
AU - Lemire, Gabrielle
AU - Ito, Yoko A.
AU - Marshall, Aren E.
AU - Chrestian, Nicolas
AU - Stanley, Valentina
AU - Brady, Lauren
AU - Tarnopolsky, Mark
AU - Curry, Cynthia J.
AU - Hartley, Taila
AU - Mears, Wendy
AU - Derksen, Alexa
AU - Rioux, Nadie
AU - Laflamme, Nataly
AU - Hutchison, Harrol T.
AU - Pais, Lynn S.
AU - Zaki, Maha S.
AU - Sultan, Tipu
AU - Dane, Adrie D.
AU - Gleeson, Joseph G.
AU - Vaz, Frédéric M.
AU - Kernohan, Kristin D.
AU - Care4Rare Canada Consortium
AU - Bernard, Geneviève
AU - Boycott, Kym M.
N1 - Funding Information: We thank the families for their participation. This work was performed under the Care4Rare Canada Consortium funded by Genome Canada and the Ontario Genomics Institute ( OGI-147 ), the Canadian Institutes of Health Research , Ontario Research Fund , Genome Alberta , Genome British Columbia , Genome Quebec , Children's Hospital of Eastern Ontario Foundation , and the Fondation Leucodystrophie . G.L. was supported by a CHAMO ( Children’s Hospital Academic Medical Organization ) clinical fellowship award through the Children’s Hospital of Eastern Ontario. A.E.M. was supported by a CIHR fellowship award ( MFE-176616 ). K.M.B. was supported by a CIHR Foundation Grant ( FDN-154279 ) and a Tier 1 Canada Research Chair in Rare Disease Precision Health. G.B. has received a Research Scholar Junior 1 award from the Fonds de Recherche du Quebec – Santé (FRQS) ( 2012-2016 ), the New Investigator Salary Award from the Canadian Institutes of Health Research ( 2017-2022 ), and a Research Scholar Senior award from the FRQS ( 2022-2025 ). Sequencing and analysis were in part provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute , the National Eye Institute , and the National Heart, Lung, and Blood Institute grant UM1 HG008900 and in part by National Human Genome Research Institute grant R01 HG009141 . Funding Information: We thank the families for their participation. This work was performed under the Care4Rare Canada Consortium funded by Genome Canada and the Ontario Genomics Institute (OGI-147), the Canadian Institutes of Health Research, Ontario Research Fund, Genome Alberta, Genome British Columbia, Genome Quebec, Children's Hospital of Eastern Ontario Foundation, and the Fondation Leucodystrophie. G.L. was supported by a CHAMO (Children's Hospital Academic Medical Organization) clinical fellowship award through the Children's Hospital of Eastern Ontario. A.E.M. was supported by a CIHR fellowship award (MFE-176616). K.M.B. was supported by a CIHR Foundation Grant (FDN-154279) and a Tier 1 Canada Research Chair in Rare Disease Precision Health. G.B. has received a Research Scholar Junior 1 award from the Fonds de Recherche du Quebec ? Sant? (FRQS) (2012-2016), the New Investigator Salary Award from the Canadian Institutes of Health Research (2017-2022), and a Research Scholar Senior award from the FRQS (2022-2025). Sequencing and analysis were in part provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung, and Blood Institute grant UM1 HG008900 and in part by National Human Genome Research Institute grant R01 HG009141. The authors declare no competing interests. Publisher Copyright: © 2021 American Society of Human Genetics
PY - 2021/10/7
Y1 - 2021/10/7
N2 - ABHD16A (abhydrolase domain-containing protein 16A, phospholipase) encodes the major phosphatidylserine (PS) lipase in the brain. PS lipase synthesizes lysophosphatidylserine, an important signaling lipid that functions in the mammalian central nervous system. ABHD16A has not yet been associated with a human disease. In this report, we present a cohort of 11 affected individuals from six unrelated families with a complicated form of hereditary spastic paraplegia (HSP) who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls. Our findings add ABHD16A to the growing list of lipid genes in which dysregulation can cause complicated forms of HSP and begin to describe the molecular etiology of this condition.
AB - ABHD16A (abhydrolase domain-containing protein 16A, phospholipase) encodes the major phosphatidylserine (PS) lipase in the brain. PS lipase synthesizes lysophosphatidylserine, an important signaling lipid that functions in the mammalian central nervous system. ABHD16A has not yet been associated with a human disease. In this report, we present a cohort of 11 affected individuals from six unrelated families with a complicated form of hereditary spastic paraplegia (HSP) who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls. Our findings add ABHD16A to the growing list of lipid genes in which dysregulation can cause complicated forms of HSP and begin to describe the molecular etiology of this condition.
KW - ABHD16A
KW - hereditary spastic paraplegia
KW - intellectual disability
KW - lysophosphatidylserine
UR - http://www.scopus.com/inward/record.url?scp=85116862838&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ajhg.2021.09.005
DO - https://doi.org/10.1016/j.ajhg.2021.09.005
M3 - Article
C2 - 34587489
SN - 0002-9297
VL - 108
SP - 2017
EP - 2023
JO - American journal of human genetics
JF - American journal of human genetics
IS - 10
ER -