SOD1-related ALS with anticipation in a large family from Martinique.
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. 2021-03-23; 22(7-8): 545-551
DOI: 10.1080/21678421.2021.1900870
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1. Amyotroph Lateral Scler Frontotemporal Degener. 2021 Nov;22(7-8):545-551. doi:
10.1080/21678421.2021.1900870. Epub 2021 Mar 23.
SOD1-related ALS with anticipation in a large family from Martinique.
Giguet-Valard AG(1), Bellance R(1), Jeannin S(1), Duclos S(1), Olive P(1),
Allard-Saint-Albin O(1), Cazeneuve C(2), Clot F(2), Sophie PV(3), Barnetche T(4),
Smith-Ravin J(5), Goizet C(6)(7).
Author information:
(1)Neurological and Neuromuscular Rare disorders department, CERCA, University
Hospital Center of Martinique, Martinique, France.
(2)University Hospital Center of Paris, La Pitié Salpétrière Hospital, Paris,
France.
(3)Genetic Department, University Hospital of Nancy, Hospital of Brabois, Nancy,
France.
(4)Rheumatology Department/FHU ACRONIM/Rare Systemic Autoimmune Diseases
Reference Center, Bordeaux University, Bordeaux, France.
(5)Research group BIOSPHERES/AREBIO, University of Antilles-Campus Schoelcher,
Martinique, France.
(6)Department of Medical Genetics, National Reference Center for Rare Diseases
‘Neurogenetic’, Pellegrin Hospital, Bordeaux University Hospital, Bordeaux,
France and.
(7)Rare Diseases Laboratory: Genetics and Metabolism (MRGM), INSERM U1211,
Bordeaux University, Bordeaux, France.
Amyotrophic Lateral Sclerosis (ALS) is a rare neurological disorder that causes
degeneration of upper and lower motor neurons and their axons. ALS is mostly
sporadic, but there are familial forms. In more than half of the familial forms,
a pathogenic variant is found in one of the following genes: C9ORF72, SOD1,
TDP-43, FUS, and VCP. SOD1 is the 2nd most common gene involved in genetic forms
of ALS. Genotype-phenotype relationships are occasionally established in genetic
forms of ALS associated with SOD1 mutations pathogenic variants. The c.281G > T
(p.[G93V]) variant in SOD1 is associated with a rarely described and unexplained
anticipation phenomenon. We report a large family from Martinique in whom ALS is
associated with a c.281G > T (p.[G93V]) pathogenic variant in SOD1 and a
statistically suggested anticipation. A whole-exome study and detection of CNVs
(CoDESeq) from 3 affected members of this family revealed the presence of
variants of uncertain signification (VUS) in other ALS genes. VUS in DCTN1 and
NEFH were present in patients of the 2nd generation, and CNVs involving UBQLN2
and C21orf2 were found in the youngest case of the family.
DOI: 10.1080/21678421.2021.1900870
PMID: 33754899 [Indexed for MEDLINE]