The latest FADS: Functional analysis of GLDN patient variants and classification of GLDN-associated AMC as a type of viable fetal akinesia deformation sequence.
arthrogryposis multiplex congenita
fetal akinesia deformation sequence
gliomedin
lethal congenital contracture syndrome 11
pulmonary hypoplasia
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:
10 2020
10 2020
Historique:
received:
17
02
2020
revised:
27
05
2020
accepted:
17
06
2020
pubmed:
20
8
2020
medline:
2
6
2021
entrez:
20
8
2020
Statut:
ppublish
Résumé
Recessive variants in the GLDN gene, which encodes the gliomedin protein and is involved in nervous system development, have recently been associated with Arthrogryposis Multiplex Congenita (AMC), a heterogenous condition characterized by congenital contractures of more than one joint. Two cohorts of patients with GLDN-associated AMC have previously been described, evolving the understanding of the condition from lethal to survivable with the provision of significant neonatal support. Here, we describe one additional patient currently living with the syndrome, having one novel variant, p.Leu365Phe, for which we provide functional data supporting its pathogenicity. We additionally provide experimental data for four other previously reported variants lacking functional evidence, including p.Arg393Lys, the second variant present in our patient. We discuss unique and defining clinical features, adding calcium-related findings which appear to be recurrent in the GLDN cohort. Finally, we compare all previously reported patients and draw new conclusions about scope of illness, with emphasis on the finding of pulmonary hypoplasia, suggesting that AMC secondary to GLDN variants may be best fitted under the umbrella of fetal akinesia deformation sequence (FADS).
Identifiants
pubmed: 32812332
doi: 10.1002/ajmg.a.61783
doi:
Substances chimiques
GLDN protein, human
0
Membrane Proteins
0
Nerve Tissue Proteins
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2291-2296Informations de copyright
© 2020 Wiley Periodicals LLC.
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