DOS Kongressen 2014 ·
165
Investigating human VANGL1, as a candidate gene
for adolescent idiopathic scoliosis
Malene Rask Andersen, Ane Simony, Lars Allan Larsen
Wilhelm Johannesen Centre for Functional Genome Research, Department of
Cellular and Molecular Medic, Københavns Universitet; Rygkirurgisk afdeling,
Middelfart Sygehus
Background:
The human VANGL1 genes has been predicted to be associat-
ed with idiopathic scoliosis, as a mutation (c.676C>T, L226F) was identified
in a family with dominant inheritance of the disease. Previous investigation of
the gene revealed the candidate to segregate, with all but one family member.
Adolescent idiopathic scoliosis (AIS) is generally considered multi-genic, but the
determining genes remain yet to be characterised.
Purpose / Aim of Study:
In this study we have examined VANGL1 as a con-
tributor to the phenotype of AIS.
Materials and Methods:
We have conducted automated Sanger sequencing of
the seven coding exons of VANGL1 gene in a disease cohort of 170 AIS patients
(n=340) and 177 controls (n=354). Localization of mutated VANGL1 proteins
were investigeted in cell systems.
Findings / Results:
Two novel mutations, each in separate individuals within
the considered disease cohort, were identified. One mutation is situated in the
third coding exon, which encodes the transmembrane parts of the VANGL pro-
tein. This mutation is a c.407T>A (L136N) conversion, for which the patient
is heterozygotes. This mutation was also identified in the dizygotic unaffect-
ed twin of the patient. The second mutation was found in the seventh coding
exon, which encode the C-terminal of the VANGL1 protein. This mutation is a
c.1318T>G (F440V) conversion, for which the patient is also heterozygotes.
Neither of the identified mutations was present in the sequenced controls or
in 2000 Danish exomes. Currently, the cellular localization of wt and mutant
VANGL1 protein are being investigated using immunofluorescence microscopy.
Conclusions:
On behalf of the current results of this study we conclude that
mutations in the VANGL1 gene may be a rare cause of AIS. Examination of the
expression of VANGL1 in teenage-adult stages of life is wanted as well as ex-
aminations of effects.
112.
