Fetal early motor neuron disruption and prenatal molecular diagnosis in a severe BICD2-opathy.
BICD2
SMALED2B
exome sequencing
motor neurons
prenatal diagnosis
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
09
01
2021
received:
09
08
2020
accepted:
22
01
2021
pubmed:
7
2
2021
medline:
10
8
2021
entrez:
6
2
2021
Statut:
ppublish
Résumé
BICD2 (BICD Cargo Adaptor 2, MIM*609797) mutations are associated with severe prenatal-onset forms of spinal muscular atrophy, lower extremity-predominant 2B (SMALED2B MIM 618291) or milder forms with childhood-onset (SMALED2A MIM 615290). Etiopathogenesis is not fully clarified and a wide spectrum of phenotypic presentations is reported, ranging from extreme prenatal forms with adverse outcome, to slow progressive late-onset forms. We report a fetus at 22 gestational weeks with evidence of Arthrogryposis Multiplex Congenita on ultrasound, presenting with fixed extended lower limbs and flexed upper limbs, bilateral clubfoot and absent fetal movements. A trio-based prenatal Exome Sequencing was performed, disclosing a de novo heterozygous pathogenic in frame deletion (NM_015250.3: c.1636_1638delAAT; p.Asn546del) in BICD2. After pregnancy termination, quantitative analysis on NeuN immunostained spinal cord sections of the ventral horns, revealed that neuronal density was markedly reduced compared to the one of an age-matched normal fetus and an age-matched type-I Spinal Muscular Atrophy sample, used as a comparative model. The present case, the first prenatally diagnosed and neuropathologically characterized, showed an early motor neuron loss in SMALED2B, providing further insight into the pathological basis of BICD2-opathies.
Identifiants
pubmed: 33547725
doi: 10.1002/ajmg.a.62111
doi:
Substances chimiques
BICD2 protein, human
0
Microtubule-Associated Proteins
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
1509-1514Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Ahmed, A. A., Skaria, P., Safina, N. P., Thiffault, I., Kats, A., Taboada, E., Habeebu, S., & Saunders, C. (2018). Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies. American Journal of Medical Genetics. Part A, 176(2), 359-367. https://doi.org/10.1002/ajmg.a.38577
Corsi, A., & Bosman, C. (1995). Adenocarcinoma and atypical carcinoid: Morphological study of a gastric collision-type tumour in the carcinoma-carcinoid spectrum. The Italian Journal of Gastroenterology, 27(6), 303-308.
Crawford, T. O. (2002). Spinal muscular atrophy. In H. R. Jones, D. C. DeVivo, & B. T. Darras (Eds.), Neuromuscular disorders of infancy and childhood, a clinician's approach. Butterworth Heinemann.
de Soccio, G., Savastano, V., Minasi, S., Bertin, S., Serafini, M., Vittori, T., Riminucci, M., & Corsi, A. (2020). Solitary juvenile xanthogranuloma of the hypopharynx. Clinico-pathologic study in a child with β-thalassemia major and cutaneous Mastocytosis. International Journal of Pediatric Otorhinolaryngology, 135(110088), 110088. https://doi.org/10.1016/j.ijporl.2020.110088
Dubowitz, V., Sewry, C., & Oldfors, A. (2021). Muscle biopsy. A practical approach (5th ed., pp. 201-213). Elsevier.
Garman, R. H. (2011). Histology of the central nervous system. Toxicologic Pathology, 39(1), 22-35. https://doi.org/10.1177/0192623310389621
Koboldt, D. C., Kastury, R. D., Waldrop, M. A., Kelly, B. J., Mosher, T. M., McLaughlin, H., Corsmeier, D., Slaughter, J. L., Flanigan, K. M., McBride, K. L., Mehta, L., Wilson, R. K., & White, P. (2018). In-frame de novo mutation in BICD2 in two patients with muscular atrophy and arthrogryposis. Cold Spring Harbor Molecular Case Studies, 4(5), a003160. https://doi.org/10.1101/mcs.a003160
Koboldt, D. C., Waldrop, M. A., Wilson, R. K., & Flanigan, K. M. (2020). The genotypic and phenotypic spectrum of BICD2 variants in spinal muscular atrophy. Annals of Neurology, 87(4), 487-496. https://doi.org/10.1002/ana.25704
Neveling, K., Martinez-Carrera, L. A., Hölker, I., Heister, A., Verrips, A., Hosseini-Barkooie, S. M., Gilissen, C., Vermeer, S., Pennings, M., Meijer, R., te Riele, M., Frijns, C. J., Suchowersky, O., MacLaren, L., Rudnik-Schöneborn, S., Sinke, R. J., Zerres, K., Lowry, R. B., Lemmink, H. H., … Wirth, B. (2013). Mutations in BICD2, which encodes a golgin and important motor adaptor, cause congenital autosomal-dominant spinal muscular atrophy. American Journal of Human Genetics, 92(6), 946-954. https://doi.org/10.1016/j.ajhg.2013.04.011
Oates, E. C., Reddel, S., Rodriguez, M. L., Gandolfo, L. C., Bahlo, M., Hawke, S. H., Lamandé, S. R., Clarke, N. F., & North, K. N. (2012). Autosomal dominant congenital spinal muscular atrophy: A true form of spinal muscular atrophy caused by early loss of anterior horn cells. Brain: A Journal of Neurology, 135(Pt 6), 1714-1723. https://doi.org/10.1093/brain/aws108
Oates, E. C., Rossor, A. M., Hafezparast, M., Gonzalez, M., Speziani, F., MacArthur, D. G., Lek, M., Cottenie, E., Scoto, M., Foley, A. R., Hurles, M., Houlden, H., Greensmith, L., Auer-Grumbach, M., Pieber, T. R., Strom, T. M., Schule, R., Herrmann, D. N., Sowden, J. E., … Reilly, M. M. (2013). Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia. American Journal of Human Genetics, 92(6), 965-973. https://doi.org/10.1016/j.ajhg.2013.04.018
Olenick, M. A., & Holzbaur, E. (2019). Dynein activators and adaptors at a glance. Journal of Cell Science, 132(6), jcs227132. https://doi.org/10.1242/jcs.227132
Palmisano, B., Spica, E., Remoli, C., Labella, R., Di Filippo, A., Donsante, S., Bini, F., Raimondo, D., Marinozzi, F., Boyde, A., Robey, P., Corsi, A., & Riminucci, M. (2019). RANKL inhibition in fibrous dysplasia of bone: A preclinical study in a mouse model of the human disease. Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research, 34(12), 2171-2182. https://doi.org/10.1002/jbmr.3828
Ravenscroft, G., Di Donato, N., Hahn, G., Davis, M. R., Craven, P. D., Poke, G., Neas, K. R., Neuhann, T. M., Dobyns, W. B., & Laing, N. G. (2016). Recurrent de novo BICD2 mutation associated with arthrogryposis multiplex congenita and bilateral perisylvian polymicrogyria. Neuromuscular Disorders: NMD, 26(11), 744-748. https://doi.org/10.1016/j.nmd.2016.09.009
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., Rehm, H. L., & ACMG Laboratory Quality Assurance Committee (2015). Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine: Official Journal of the American College of Medical Genetics, 17(5), 405-424. https://doi.org/10.1038/gim.2015.30
Rossor, A. M., Oates, E. C., Salter, H. K., Liu, Y., Murphy, S. M., Schule, R., Gonzalez, M. A., Scoto, M., Phadke, R., Sewry, C. A., Houlden, H., Jordanova, A., Tournev, I., Chamova, T., Litvinenko, I., Zuchner, S., Herrmann, D. N., Blake, J., Sowden, J. E., … North, K. N. (2015). Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Brain: A Journal of Neurology, 138(Pt 2), 293-310. https://doi.org/10.1093/brain/awu356
Rossor, A. M., Sleigh, J. N., Groves, M., Muntoni, F., Reilly, M. M., Hoogenraad, C. C., & Schiavo, G. (2020). Loss of BICD2 in muscle drives motor neuron loss in a developmental form of spinal muscular atrophy. Acta Neuropathologica Communications, 8(1), 34. https://doi.org/10.1186/s40478-020-00909-6
Skaria, P., Dahl, A., & Ahmed, A. (2019). Arthrogryposis multiplex congenita in utero: Radiologic and pathologic findings. The Journal of Maternal-Fetal & Neonatal Medicine: the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 32(3), 502-511. https://doi.org/10.1080/14767058.2017.1381683
Soler-Botija, C., Ferrer, I., Gich, I., Baiget, M., & Tizzano, E. F. (2002). Neuronal death is enhanced and begins during foetal development in type I spinal muscular atrophy spinal cord. Brain: A Journal of Neurology, 125(Pt 7), 1624-1634. https://doi.org/10.1093/brain/awf155
Storbeck, M., Horsberg Eriksen, B., Unger, A., Hölker, I., Aukrust, I., Martínez-Carrera, L. A., Linke, W. A., Ferbert, A., Heller, R., Vorgerd, M., Houge, G., & Wirth, B. (2017). Phenotypic extremes of BICD2-opathies: From lethal, congenital muscular atrophy with arthrogryposis to asymptomatic with subclinical features. European Journal of Human Genetics: EJHG, 25(9), 1040-1048. https://doi.org/10.1038/ejhg.2017.98
Unger, A., Dekomien, G., Güttsches, A., Dreps, T., Kley, R., Tegenthoff, M., Ferbert, A., Weis, J., Heyer, C., Linke, W. A., Martinez-Carrera, L., Storbeck, M., Wirth, B., Hoffjan, S., & Vorgerd, M. (2016). Expanding the phenotype of BICD2 mutations toward skeletal muscle involvement. Neurology, 87(21), 2235-2243. https://doi.org/10.1212/WNL.0000000000003360