A novel MBD5 mutation in an intellectually disabled adult female patient with epilepsy: Suggestive of early onset dementia?
MBD5
MAND
autism
epilepsy
intellectual disability
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
14
04
2019
revised:
27
05
2019
accepted:
05
06
2019
pubmed:
11
7
2019
medline:
1
7
2020
entrez:
11
7
2019
Statut:
ppublish
Résumé
The minimal critical region in 2q23.1 deletion syndrome comprises one gene only, that is, the methyl-CpG-binding domain protein 5 (MBD5) gene. Since the phenotypes of patients with deletions, duplications or pathogenic variants of MBD5 show considerable overlap, the term MBD5-associated neurodevelopmental disorder (MAND) was proposed. These syndromes are characterized by intellectual disability, seizures of any kind and symptoms from the autism spectrum. In a very limited number of patients, MAND may be associated with regression starting either at early infancy or at midlife. The present paper describes a severely intellectually disabled autistic female with therapy resistant complex partial epilepsy starting at her 16the with gradual cognitive and behavioral regression towards her sixth decade. Cognitive and behavioral regression occurred towards the patient's sixth decade. Exome sequencing disclosed a novel heterozygous pathogenic frameshift mutation of MBD5 that was considered to be causative for the combination of intellectual disability, treatment-resistant epilepsy and autism. The presented patient is the second with a pathogenic MBD5 mutation in whom the course of disease is suggestive of early onset dementia starting in her fifth decade. These findings stress the importance of exome sequencing, also in elderly intellectually disabled patients, particularly in those with autism.
Sections du résumé
BACKGROUND
The minimal critical region in 2q23.1 deletion syndrome comprises one gene only, that is, the methyl-CpG-binding domain protein 5 (MBD5) gene. Since the phenotypes of patients with deletions, duplications or pathogenic variants of MBD5 show considerable overlap, the term MBD5-associated neurodevelopmental disorder (MAND) was proposed. These syndromes are characterized by intellectual disability, seizures of any kind and symptoms from the autism spectrum. In a very limited number of patients, MAND may be associated with regression starting either at early infancy or at midlife.
METHODS
The present paper describes a severely intellectually disabled autistic female with therapy resistant complex partial epilepsy starting at her 16the with gradual cognitive and behavioral regression towards her sixth decade.
RESULTS
Cognitive and behavioral regression occurred towards the patient's sixth decade. Exome sequencing disclosed a novel heterozygous pathogenic frameshift mutation of MBD5 that was considered to be causative for the combination of intellectual disability, treatment-resistant epilepsy and autism.
CONCLUSION
The presented patient is the second with a pathogenic MBD5 mutation in whom the course of disease is suggestive of early onset dementia starting in her fifth decade. These findings stress the importance of exome sequencing, also in elderly intellectually disabled patients, particularly in those with autism.
Identifiants
pubmed: 31290275
doi: 10.1002/mgg3.849
pmc: PMC6687664
doi:
Substances chimiques
DNA-Binding Proteins
0
MBD5 protein, human
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e849Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
Références
Transl Psychiatry. 2015 May 12;5:e565
pubmed: 25966365
Eur J Hum Genet. 2014 Jan;22(1):57-63
pubmed: 23632792
Am J Hum Genet. 2012 Jul 13;91(1):73-82
pubmed: 22726846
Eur J Hum Genet. 2013 Dec;21(12):1457-61
pubmed: 23422940
Eur J Hum Genet. 2016 Aug;24(9):1376
pubmed: 27514998
Mol Psychiatry. 2014 Mar;19(3):368-79
pubmed: 23587880
Am J Hum Genet. 2011 Oct 7;89(4):551-63
pubmed: 21981781
Am J Hum Genet. 2003 Dec;73(6):1261-70
pubmed: 14628292
Int J Mol Sci. 2015 Apr 07;16(4):7627-43
pubmed: 25853262
J Neurosci. 2017 Nov 8;37(45):10773-10782
pubmed: 29118205
Eur J Hum Genet. 2010 Apr;18(4):436-41
pubmed: 19904302
Am J Med Genet A. 2011 Feb;155A(2):424-9
pubmed: 21271666
Eur J Med Genet. 2012 Jan;55(1):59-62
pubmed: 22085995
PLoS One. 2010 Aug 06;5(8):e11982
pubmed: 20700456
Eur J Hum Genet. 2015 Jun;23(6):781-9
pubmed: 25271084
Mol Genet Genomic Med. 2019 Aug;7(8):e849
pubmed: 31290275
PLoS Genet. 2017 Oct 25;13(10):e1006864
pubmed: 29069077
Eur J Hum Genet. 2010 Feb;18(2):163-70
pubmed: 19809484