Abstract
Horizontal gaze palsy and progressive scoliosis (HGPPS) is an autosomal recessive
neurologic disorder caused by homozygous or compound heterozygous mutations in the
ROBO3 gene on chromosome 11. We clinically evaluated seven individuals with HGPPS from
five previously unreported consanguineous families. We sequenced ROBO3 in all affected individuals, additional unaffected members of each family, and ethnic
controls. All affected individuals had severe horizontal gaze restriction, progressive
scoliosis, and lower brainstem hypoplasia on neuroimaging, the hallmarks of this syndrome.
One individual experienced head trauma with a right subdural hematoma associated with
a right hemiparesis, observations that confirm clinically for the first time that
corticospinal tracts in HGPPS are uncrossed. We found five novel homozygous ROBO3 mutations (four missense mutations and one base deletion) distributed throughout
the extracellular domain of the gene. The ROBO3 gene does not appear to have an obvious hot spot area for mutations; therefore, we
recommend sequencing all exons and exon–intron boundaries in patients with clinical
and/or radiologic features of HGPPS.
Abbreviations:
HGPPS (Horizontal gaze palsy and progressive scoliosis), MEP (Motor evoked potentials), SSEP (Somatosensory evoked potentials)Keywords
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Article info
Publication history
Accepted:
August 19,
2008
Received in revised form:
August 17,
2008
Received:
April 6,
2008
Identification
Copyright
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
