Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease
(2021) In Annals of Clinical and Translational Neurology 8(11). p.2155-2165- Abstract
Objective: To delineate the full phenotypic spectrum of BCS1L-related disease, provide better understanding of the genotype–phenotype correlations and identify reliable prognostic disease markers. Methods: We performed a retrospective multinational cohort study of previously unpublished patients followed in 15 centres from 10 countries. Patients with confirmed biallelic pathogenic BCS1L variants were considered eligible. Clinical, laboratory, neuroimaging and genetic data were analysed. Patients were stratified into different groups based on the age of disease onset, whether homozygous or compound heterozygous for the c.232A>G (p.Ser78Gly) variant, and those with other pathogenic BCS1L variants. Results: Thirty-three patients were... (More)
Objective: To delineate the full phenotypic spectrum of BCS1L-related disease, provide better understanding of the genotype–phenotype correlations and identify reliable prognostic disease markers. Methods: We performed a retrospective multinational cohort study of previously unpublished patients followed in 15 centres from 10 countries. Patients with confirmed biallelic pathogenic BCS1L variants were considered eligible. Clinical, laboratory, neuroimaging and genetic data were analysed. Patients were stratified into different groups based on the age of disease onset, whether homozygous or compound heterozygous for the c.232A>G (p.Ser78Gly) variant, and those with other pathogenic BCS1L variants. Results: Thirty-three patients were included. We found that growth failure, lactic acidosis, tubulopathy, hepatopathy and early death were more frequent in those with disease onset within the first month of life. In those with onset after 1 month, neurological features including movement disorders and seizures were more frequent. Novel phenotypes, particularly involving movement disorder, were identified in this group. The presence of the c.232A>G (p.Ser78Gly) variant was associated with significantly worse survival and exclusively found in those with disease onset within the first month of life, whilst other pathogenic BCS1L variants were more frequent in those with later symptom onset. Interpretation: The phenotypic spectrum of BCS1L-related disease comprises a continuum of clinical features rather than a set of separate syndromic clinical identities. Age of onset defines BCS1L-related disease clinically and early presentation is associated with poor prognosis. Genotype correlates with phenotype in the presence of the c.232A>G (p.Ser78Gly) variant.
(Less)
- author
- Hikmat, Omar
; Isohanni, Pirjo
; Keshavan, Nandaki
; Ferla, Matteo P.
; Fassone, Elisa
; Abbott, Mary Alice
; Bellusci, Marcello
; Darin, Niklas
; Dimmock, David
; Ghezzi, Daniele
; Houlden, Henry
; Invernizzi, Federica
; Kamarus Jaman, Nazreen B.
; Kurian, Manju A.
; Morava, Eva
; Naess, Karin
; Ortigoza-Escobar, Juan Darío
; Parikh, Sumit
; Pennisi, Alessandra
; Barcia, Giulia
; Tylleskär, Karin B.
; Brackman, Damien
; Wortmann, Saskia B.
; Taylor, Jenny C.
; Bindoff, Laurence A.
; Fellman, Vineta
LU
and Rahman, Shamima
(Less) - organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Annals of Clinical and Translational Neurology
- volume
- 8
- issue
- 11
- pages
- 2155 - 2165
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85117223798
- pmid:34662929
- ISSN
- 2328-9503
- DOI
- 10.1002/acn3.51470
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association
- id
- 91923fb2-2551-4bc0-b6e5-b9e54ab67190
- date added to LUP
- 2021-11-05 15:19:19
- date last changed
- 2024-06-16 22:32:26
@article{91923fb2-2551-4bc0-b6e5-b9e54ab67190,
abstract = {{<p>Objective: To delineate the full phenotypic spectrum of BCS1L-related disease, provide better understanding of the genotype–phenotype correlations and identify reliable prognostic disease markers. Methods: We performed a retrospective multinational cohort study of previously unpublished patients followed in 15 centres from 10 countries. Patients with confirmed biallelic pathogenic BCS1L variants were considered eligible. Clinical, laboratory, neuroimaging and genetic data were analysed. Patients were stratified into different groups based on the age of disease onset, whether homozygous or compound heterozygous for the c.232A>G (p.Ser78Gly) variant, and those with other pathogenic BCS1L variants. Results: Thirty-three patients were included. We found that growth failure, lactic acidosis, tubulopathy, hepatopathy and early death were more frequent in those with disease onset within the first month of life. In those with onset after 1 month, neurological features including movement disorders and seizures were more frequent. Novel phenotypes, particularly involving movement disorder, were identified in this group. The presence of the c.232A>G (p.Ser78Gly) variant was associated with significantly worse survival and exclusively found in those with disease onset within the first month of life, whilst other pathogenic BCS1L variants were more frequent in those with later symptom onset. Interpretation: The phenotypic spectrum of BCS1L-related disease comprises a continuum of clinical features rather than a set of separate syndromic clinical identities. Age of onset defines BCS1L-related disease clinically and early presentation is associated with poor prognosis. Genotype correlates with phenotype in the presence of the c.232A>G (p.Ser78Gly) variant.</p>}},
author = {{Hikmat, Omar and Isohanni, Pirjo and Keshavan, Nandaki and Ferla, Matteo P. and Fassone, Elisa and Abbott, Mary Alice and Bellusci, Marcello and Darin, Niklas and Dimmock, David and Ghezzi, Daniele and Houlden, Henry and Invernizzi, Federica and Kamarus Jaman, Nazreen B. and Kurian, Manju A. and Morava, Eva and Naess, Karin and Ortigoza-Escobar, Juan Darío and Parikh, Sumit and Pennisi, Alessandra and Barcia, Giulia and Tylleskär, Karin B. and Brackman, Damien and Wortmann, Saskia B. and Taylor, Jenny C. and Bindoff, Laurence A. and Fellman, Vineta and Rahman, Shamima}},
issn = {{2328-9503}},
language = {{eng}},
number = {{11}},
pages = {{2155--2165}},
publisher = {{Wiley-Blackwell}},
series = {{Annals of Clinical and Translational Neurology}},
title = {{Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease}},
url = {{http://dx.doi.org/10.1002/acn3.51470}},
doi = {{10.1002/acn3.51470}},
volume = {{8}},
year = {{2021}},
}