A patient with novel MBOAT7 variant: The cerebellar atrophy is progressive and displays a peculiar neurometabolic profile.
Acyltransferases
/ genetics
Adolescent
Adult
Cerebellum
/ diagnostic imaging
Child
Consanguinity
Exome
/ genetics
Female
Genetic Predisposition to Disease
Homozygote
Humans
Intellectual Disability
/ genetics
Male
Membrane Proteins
/ genetics
Olivopontocerebellar Atrophies
/ genetics
Pedigree
Exome Sequencing
Young Adult
MBOAT7
cerebellar atrophy
consanguinity
hydrogen-magnetic resonance spectroscopy
intellectual disability
review
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:
23
03
2020
revised:
13
05
2020
accepted:
30
05
2020
pubmed:
4
8
2020
medline:
2
6
2021
entrez:
4
8
2020
Statut:
ppublish
Résumé
Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5-year-old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole-exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen-magnetic resonance spectroscopy (H-MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7-related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth.
Identifiants
pubmed: 32744787
doi: 10.1002/ajmg.a.61773
doi:
Substances chimiques
Membrane Proteins
0
Acyltransferases
EC 2.3.-
MBOAT7 protein, human
EC 2.3.-
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
2377-2383Informations de copyright
© 2020 Wiley Periodicals LLC.
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