Horizontal gaze palsy with progressive scoliosis can result from compound heterozygous mutations in ROBO3.
BACKGROUND
Horizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disorder characterised by congenital absence of horizontal gaze, progressive scoliosis, and failure of the corticospinal and somatosensory axon tracts to decussate in the medulla. We previously reported that HGPPS patients from consanguineous pedigrees harbour homozygous mutations in the axon guidance molecule ROBO3.


METHODS
We now report two sporadic HGPPS children of non-consanguineous parents who harbour compound heterozygous mutations in ROBO3. The mother of one of the children also had scoliosis DNA was extracted from a blood sample from each participant using a standard protocol, and the coding exons of ROBO3 were amplified and sequenced as previously described.


RESULTS
Each patient harboured two unique heterozygous mutations in ROBO3, having inherited one mutation from each parent.


CONCLUSIONS
HGPPS can result from compound heterozygous mutations. More comprehensive examinations of parents and siblings of HGPPS patients are required to determine if the incidence of scoliosis in individuals harbouring heterozygous ROBO3 mutations is greater than in the general population.
Chan
W-M
WM
Traboulsi
E I
EI
Arthur
B
B
Friedman
N
N
Andrews
C
C
Engle
E C
EC
D002648:Child; D002658:Developmental Disabilities / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D015835:Ocular Motility Disorders / Q000235:genetics*; D010375:Pedigree; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000235:genetics*; D012600:Scoliosis / Q000235:genetics* / Q000503:physiopathology; D000097905:Roundabout Proteins
D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C499630:ROBO3 protein, human; D000097905:Roundabout Proteins