The recurrent TUBB3 Gly98Ser substitution is the first described to inconsistently result in CFEOM3.
Adult
Amino Acid Substitution
/ genetics
Child
Eye Diseases, Hereditary
/ diagnostic imaging
Female
Fibrosis
/ diagnostic imaging
Genotype
Humans
Infant
Male
Malformations of Cortical Development
/ diagnostic imaging
Mutation, Missense
/ genetics
Neuroimaging
Ophthalmoplegia
/ diagnostic imaging
Pedigree
Tubulin
/ genetics
TUBB3 Gly98Ser
congenital fibrosis of the extraocular muscles
genotype-phenotype comparison
malformations of cortical development
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:
09 2020
09 2020
Historique:
received:
09
03
2020
revised:
02
06
2020
accepted:
05
06
2020
pubmed:
25
7
2020
medline:
9
6
2021
entrez:
25
7
2020
Statut:
ppublish
Résumé
Missense variants in TUBB3 have historically been associated with either congenital fibrosis of the extraocular muscles type 3 (CFEOM3) or malformations of cortical development (MCD). Until a recent report identified two amino acid substitutions in four patients that had clinical features of both disorders, pathogenic variants of TUBB3 were thought distinct to either respective disorder. Three recurrent de novo Gly71Arg TUBB3 substitutions and a single patient with a de novo Gly98Ser substitution blurred the MCD and CFEOM3 phenotypic distinctions. Here we report a second patient with a missense c.292G>A (p.Gly98Ser) substitution, but without CFEOM3, the first reported evidence that even the same TUBB3 substitution can produce a spectrum of TUBB3 syndrome phenotypes. Our patient presented with amblyopia, exotropia, optic disc pallor, and developmental delay. Neuroimaging identified hypoplasia of the corpus callosum, interdigitation of the frontal lobe gyri, and dysplasia or hypoplasia of the optic nerves, basal ganglia, brainstem, and cerebellum. This report identifies the TUBB3 Gly98Ser substitution to be recurrent but inconsistently including CFEOM3, and identifies the absence of joint contractures and the presence of optic disc abnormalities that may be genotype-specific to the TUBB3 Gly98Ser substitution.
Identifiants
pubmed: 32705776
doi: 10.1002/ajmg.a.61747
doi:
Substances chimiques
TUBB3 protein, human
0
Tubulin
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
2161-2167Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
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