Revertant mosaicism in junctional epidermolysis bullosa due to multiple correcting second-site mutations in LAMB3.

[junctional epidermolysis bullosa]

Revertant mosaicism due to in vivo reversion of an inherited mutation has been described in the genetic skin disease epidermolysis bullosa (EB ) for the genes KRT 14 and COL 17 A 1 . Here we demonstrate the presence of multiple second -site mutations , all correcting the germline mutation LAMB 3 :c .628 G-->A ;p .E 210 K , in 2 unrelated non-Herlitz junctional EB patients with revertant mosaicism . Both probands had a severe reduction in laminin-332 expression in their affected skin . Remarkably , the skin on the lower leg of patient 078 -01 (c .628 G-->A /c .1903 C-->T ) became progressively clinically healthy , with normal expression of laminin-332 on previously affected skin . In the other proband , 029 -01 (c .628 G-->A /c .628 G-->A ), the revertant patches were located at his arms , shoulder , and chest . DNA analysis showed different second -site mutations in revertant keratinocytes of distinct biopsy specimens (c .565 -3 T -->C , c .596 G-->C ;p .G 199 A , c .619 A-->C ;p .K 207 Q , c .628 +42 G-->A , and c .629 -1 G-->A ), implying that there is not a single preferred mechanism for the correction of a specific mutation . Our data offer prospects for EB treatment in particular cases , since revertant mosaicism seems to occur at a higher frequency than expected . This opens the possibility of applying revertant cell therapy in mosaic EB of the LAMB 3 gene by using autologous naturally corrected keratinocytes , thereby bypassing the recombinant gene correction phase .

Diseases
Validation

Diseases presenting "multiple second-site mutations" symptom

junctional epidermolysis bullosa

omenn syndrome

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