HUWE1 mutations in Juberg-Marsidi and Brooks syndromes: the results of an X-chromosome exome sequencing study.
BMJ Open
; 6(4): e009537, 2016 Apr 29.
Article
in En
| MEDLINE
| ID: mdl-27130160
ABSTRACT
BACKGROUND:
X linked intellectual disability (XLID) syndromes account for a substantial number of males with ID. Much progress has been made in identifying the genetic cause in many of the syndromes described 20-40â years ago. Next generation sequencing (NGS) has contributed to the rapid discovery of XLID genes and identifying novel mutations in known XLID genes for many of these syndromes.METHODS:
2 NGS approaches were employed to identify mutations in X linked genes in families with XLID disorders. 1 involved exome sequencing of genes on the X chromosome using the Agilent SureSelect Human X Chromosome Kit. The second approach was to conduct targeted NGS sequencing of 90 known XLID genes.RESULTS:
We identified the same mutation, a c.12928 G>C transversion in the HUWE1 gene, which gives rise to a p.G4310R missense mutation in 2 XLID disorders Juberg-Marsidi syndrome (JMS) and Brooks syndrome. Although the original families with these disorders were considered separate entities, they indeed overlap clinically. A third family was also found to have a novel HUWE1 mutation.CONCLUSIONS:
As we identified a HUWE1 mutation in an affected male from the original family reported by Juberg and Marsidi, it is evident the syndrome does not result from a mutation in ATRX as reported in the literature. Additionally, our data indicate that JMS and Brooks syndromes are allelic having the same HUWE1 mutation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromosomes, Human, X
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Deafness
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Mental Retardation, X-Linked
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Ubiquitin-Protein Ligases
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Growth Disorders
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Hypogonadism
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Muscle Spasticity
Limits:
Adolescent
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Adult
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Child
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Humans
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Male
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Middle aged
Language:
En
Journal:
BMJ Open
Year:
2016
Document type:
Article
Affiliation country: