Hereditary multiple exostoses (HME) is a rare skeletal disorder characterized by
the formation of multiple benign cartilage-capped tumors, usually in the
metaphyseal region of the long bones. Over 70% of HME cases arise from
monoallelic mutations in either of the two genes encoding the heparan sulfate
(HS) synthesis enzymes,
ext1
and
ext2
. To
identify more HME-associated mutations, genomic DNA from members of five
independent consanguineous families with HME was sequenced with whole exome
sequencing (WES). A novel heterozygous splice site mutation (c.1173+2T>A) in
ext2
was detected in all three affected members of family
V. Further study showed that the novel mutation caused exon 7 of
ext2
mRNA to be skipped during splicing and caused a
frameshift after the codon for Arg360, which results in the appearance of new 43
codons, followed by a termination codon. Although the resulting truncated
protein was still localized to the Golgi, similar to the full-length EXT2, its
HS synthesis activity decreased by 40%. In this study, a novel splice site
mutation in
ext2
was identified and suggested to be a
pathogenic mutation of HME, which may expand the genetic etiology spectrum of
HME and may be helpful for clinical genetic counseling and prenatal
diagnosis.
There is a paucity of data describing sagittal alignment changes in children with congenital scoliosis (CS) treated by hemivertebra (HV) resection. This study aimed to evaluate the effects of posterior HV resection on spine sagittal alignment in children with CS. This is a retrospective analysis of 31 children with CS (mean age at surgery: 49.61 ± 10.21 months; range, 39-72; mean follow-up time: 5.16 ± 1.21 years; range: 3-7) treated at our Institution. Only patients with single thoracic or single lumbar, fully segmented HV managed by posterior HV resection and two segments fusion with four screws and two robs were included. According to the anatomical location of the HV, patients were divided into two groups: thoracic (group A) and lumbar (group B). Thoracic kyphosis (T1-T12; TK) and lumbar lordosis (L1-S1; LL) were measured pre-and postoperatively at 6 months interval. Postoperative TK and LL were 30.3 ± 11.47 and 28.8 ± 9.47, and were 31.98 ± 9.66 and 46.7 ± 11.37 at the last follow-up visit, respectively. The incidence of thoracic hypokyphosis in group B was 53.3%, and it was significantly higher compared to group A (12.5%, P = 0.04). During follow-up, TK changes were comparable between the two groups of patients while LL improved in all patients 6 months after surgery, and continued to improve thereafter. Posterior HV resection and short segment fusion have limited impact on the evolution of TK; in particular, children with lumbar HV were more likely to be hypokyphotic preoperatively, but less likely postoperatively with an increase in LL and a stabilization of TK.
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