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Title: Harlequin ichthyosis and ABCA12
Author: Rajpopat, Shefali
ISNI:       0000 0004 2731 0316
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2012
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Harlequin ichthyosis (HI), a rare severe form of congenital ichthyosis is caused by recessive mutations in the ABCA12 gene. At birth, affected neonates have widespread, grossly thickened skin, separated by deep red fissures, bilateral ectropion, eclabium and a rudimentary nose and ears. Previously, most babies died shortly after birth but with improved neonatal care and the early introduction of oral retinoids, there is now a cohort of HI survivors. ABCA12 mutation analysis was performed and bi-allelic mutations were identified in 14 out of 17 cases, 9 of which were novel. In one consanguineous case, reverse transcriptase PCR on a parental skin biopsy and copy number analysis were used to identify a multiple exon deletion, when standard techniques failed. A previous study showed that in ABCA12 deficiency, epidermal differentiation is dysregulated. Staining of skin biopsies with RXR-α and PPAR-δ showed that both of these nuclear hormone receptors are up-regulated in the spinous and granular cell layers of HI skin compared to normal skin while ABCA1 is down regulated in the basal layer. The largest review to date of the outcomes of babies born with HI was performed. A retrospective clinical questionnaire was completed for 45 patients worldwide. Survivors’ ages ranged from 10 months to 25 years with an overall survival rate of 55.6%. Death usually occurred in the first 3 months and was attributed to sepsis and/or respiratory failure in 75% if cases. The early introduction of oral retinoids may improve survival as 83% of those treated survived, whereas 76% who were not given retinoids died. Recurrent skin infections in infancy affected one third. Problems maintaining weight affected 44%. Three children developed an inflammatory arthritis and developmental delay was reported in 32%. Mutation analysis revealed that 52% of survivors had compound heterozygous mutations whereas all deaths were associated with homozygous mutations.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine