Systematic data-querying of large pediatric biorepository identifies novel Ehlers-Danlos Syndrome variant.
BMC Musculoskelet Disord
; 17: 80, 2016 Feb 16.
Article
en En
| MEDLINE
| ID: mdl-26879370
ABSTRACT
BACKGROUND:
Ehlers Danlos Syndrome is a rare form of inherited connective tissue disorder, which primarily affects skin, joints, muscle, and blood cells. The current study aimed at finding the mutation that causing EDS type VII C also known as "Dermatosparaxis" in this family.METHODS:
Through systematic data querying of the electronic medical records (EMRs) of over 80,000 individuals, we recently identified an EDS family that indicate an autosomal dominant inheritance. The family was consented for genomic analysis of their de-identified data. After a negative screen for known mutations, we performed whole genome sequencing on the male proband, his affected father, and unaffected mother. We filtered the list of non-synonymous variants that are common between the affected individuals.RESULTS:
The analysis of non-synonymous variants lead to identifying a novel mutation in the ADAMTSL2 (p. Gly421Ser) gene in the affected individuals. Sanger sequencing confirmed the mutation.CONCLUSION:
Our work is significant not only because it sheds new light on the pathophysiology of EDS for the affected family and the field at large, but also because it demonstrates the utility of unbiased large-scale clinical recruitment in deciphering the genetic etiology of rare mendelian diseases. With unbiased large-scale clinical recruitment we strive to sequence as many rare mendelian diseases as possible, and this work in EDS serves as a successful proof of concept to that effect.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Variación Genética
/
Bases de Datos Genéticas
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Síndrome de Ehlers-Danlos
/
Proteínas ADAM
/
Minería de Datos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
BMC Musculoskelet Disord
Asunto de la revista:
FISIOLOGIA
/
ORTOPEDIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos