Evidence of mosaicism in SPAST variant carriers in four French families
Eur J Hum Genet. 2021-05-06; 29(7): 1158-1163
DOI: 10.1038/S41431-021-00847-4
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Angelini C(1)(2), Goizet C(1)(2)(3), Said SA(4), Camu W(5), Depienne C(4)(6)(7), Heron B(8), Kol B(4), Guillaud-Bataille M(4), Pennamen P(1)(3), Rooryck C(1)(3), Scherer-Gagou C(9), Tissier L(4), Stevanin G(4)(6)(10), Leguern E(11)(12), Banneau G(4)(13).
Author information:
(1)Service de Génétique Médicale, CHU Bordeaux, Bordeaux, Bordeaux, France.
(2)Centre de Référence Maladies Rares Neurogénétique, Service de Génétique Médicale, Bordeaux, France.
(3)INSERM U1211, laboratoire MRGM, Univ. Bordeaux, Bordeaux, France.
(4)Sorbonne Université, AP-HP, GH Pitié-Salpêtrière, Département de génétique, Paris, France.
(5)Centre de référence SLA, explorations neurologiques, CHU et Univ Montpellier, Montpellier, France.
(6)Sorbonne université, Institut du Cerveau, INSERM U 1127, Paris, France.
(7)Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
(8)Service de Neurologie Pédiatrique, Hôpital Armand Trousseau-La Roche Guyon, GHUEP, APHP, Paris, France.
(9)Centre National de Référence pour les Maladies Neurogénétiques de l’Adulte, Département de Neurologie, Centre Hospitalier Universitaire d’Angers, Angers, France.
(10)Equipe de neurogénétique, Ecole Pratique des Hautes Etudes (EPHE), PSL Research University, Paris, France.
(11)Sorbonne Université, AP-HP, GH Pitié-Salpêtrière, Département de génétique, Paris, France. .
(12)Sorbonne université, Institut du Cerveau, INSERM U 1127, Paris, France. .
(13)Département de Génétique Médicale, Institut Fédératif de Biologie, Hôpital Purpan, Toulouse, France.
Hereditary spastic paraplegias (HSP) are heterogeneous disorders, with more than 70 causative genes. Variants in SPAST are the most frequent genetic etiology and are responsible for spastic paraplegia type 4 (SPG4). Age at onset can vary, even
between patients from the same family, and incomplete penetrance is described. Somatic mosaicism is extremely rare with only three patients reported in the literature. We report here SPAST mosaic variants in four unrelated patients. We confirm that mosaicism in SPAST is a very rare event with only four identified cases on more than 300 patients with a SPAST variant previously described by our clinical diagnostic laboratory.
© 2021. The Author(s), under exclusive licence to European Society of Human Genetics.