BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia.
Am J Hum Genet
; 98(6): 1243-1248, 2016 06 02.
Article
in En
| MEDLINE
| ID: mdl-27236923
ABSTRACT
Spondyloepimetaphyseal dysplasias (SEMDs) comprise a heterogeneous group of autosomal-dominant and autosomal-recessive disorders. An apparent X-linked recessive (XLR) form of SEMD in a single Italian family was previously reported. We have been able to restudy this family together with a second family from Korea by segregating a severe SEMD in an X-linked pattern. Exome sequencing showed missense mutations in BGN c.439A>G (p.Lys147Glu) in the Korean family and c.776G>T (p.Gly259Val) in the Italian family; the c.439A>G (p.Lys147Glu) mutation was also identified in a further simplex SEMD case from India. Biglycan is an extracellular matrix proteoglycan that can bind transforming growth factor beta (TGF-ß) and thus regulate its free concentration. In 3-dimensional simulation, both altered residues localized to the concave arc of leucine-rich repeat domains of biglycan that interact with TGF-ß. The observation of recurrent BGN mutations in XLR SEMD individuals from different ethnic backgrounds allows us to define "XLR SEMD, BGN type" as a nosologic entity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteochondrodysplasias
/
Genetic Diseases, X-Linked
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Biglycan
/
Mutation
Type of study:
Prognostic_studies
Limits:
Adult
/
Aged
/
Child
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Child, preschool
/
Female
/
Humans
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Infant
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Male
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Middle aged
/
Newborn
Language:
En
Journal:
Am J Hum Genet
Year:
2016
Type:
Article