Characterization of large deletions of the MECP2 gene in Rett syndrome patients by gene dosage analysis.
Adolescent
Alleles
Child
Child, Preschool
DNA Mutational Analysis
Female
Forkhead Transcription Factors
/ genetics
Gene Dosage
Genetic Association Studies
Genotype
Humans
Methyl-CpG-Binding Protein 2
/ genetics
Nerve Tissue Proteins
/ genetics
Phenotype
Protein Serine-Threonine Kinases
/ genetics
Rett Syndrome
/ diagnosis
Sequence Deletion
MECP2
Phenotype-genotype correlations
Rett syndrome
large deletions
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:
24
08
2018
revised:
24
01
2019
accepted:
16
05
2019
pubmed:
18
6
2019
medline:
23
6
2020
entrez:
18
6
2019
Statut:
ppublish
Résumé
Rett syndrome (RTT) is a developmental disorder with an early onset and X-linked dominant inheritance pattern. It is first recognized in infancy and is seen almost always in girls, but it may be seen in boys on rare occasions. Typical RTT is caused by de novo mutations of the gene MECP2 (OMIM*300005), and atypical forms of RTT can be caused by mutations of the CDKL5 (OMIM*300203) and FOXG1 (OMIM*164874) genes. Approximately 5% of the mutations detected in MECP2 are large rearrangements that range from exons to the entire gene. Here, we have characterized the deletions detected by multiplex ligation-dependent probe amplification (MLPA) in the gene MECP2 of 21 RTT patients. Breakpoints were delineated by DNA-qPCR until the amplification of the deleted allele by long-PCR was possible. This methodology enabled us to characterize deletions ranging from 1,235 bp to 85 kb, confirming the partial or total deletion of the MECP2 gene in all these patients. Additionally, our cases support the evidence claiming that most of these breakpoints occur in some restricted regions of the MECP2 gene. These molecular data together with the clinical information enable us to propose a genotype-phenotype correlation, which is essential for providing genetic counseling.
Sections du résumé
BACKGROUND
Rett syndrome (RTT) is a developmental disorder with an early onset and X-linked dominant inheritance pattern. It is first recognized in infancy and is seen almost always in girls, but it may be seen in boys on rare occasions. Typical RTT is caused by de novo mutations of the gene MECP2 (OMIM*300005), and atypical forms of RTT can be caused by mutations of the CDKL5 (OMIM*300203) and FOXG1 (OMIM*164874) genes.
METHODS
Approximately 5% of the mutations detected in MECP2 are large rearrangements that range from exons to the entire gene. Here, we have characterized the deletions detected by multiplex ligation-dependent probe amplification (MLPA) in the gene MECP2 of 21 RTT patients. Breakpoints were delineated by DNA-qPCR until the amplification of the deleted allele by long-PCR was possible.
RESULTS
This methodology enabled us to characterize deletions ranging from 1,235 bp to 85 kb, confirming the partial or total deletion of the MECP2 gene in all these patients. Additionally, our cases support the evidence claiming that most of these breakpoints occur in some restricted regions of the MECP2 gene.
CONCLUSION
These molecular data together with the clinical information enable us to propose a genotype-phenotype correlation, which is essential for providing genetic counseling.
Identifiants
pubmed: 31206249
doi: 10.1002/mgg3.793
pmc: PMC6687651
doi:
Substances chimiques
FOXG1 protein, human
0
Forkhead Transcription Factors
0
MECP2 protein, human
0
Methyl-CpG-Binding Protein 2
0
Nerve Tissue Proteins
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
CDKL5 protein, human
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e793Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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