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• The D982G missense mutation in LAMB3 is unlikely to cause junctional epidermolysis bullosa
  Lauren C Briere
  Published on: 27 April 2016

• Published on: 27 April 2016

  The D982G missense mutation in LAMB3 is unlikely to cause junctional epidermolysis bullosa

  • Lauren C Briere, Genetic Counselor

  We found this paper to be immensely informative while researching junctional epidermolysis bullosa (JEB) for a particular clinical case, which is described below. During the course of testing for this particular case we found evidence suggesting that that the D982G mutation in LAMB3 may not be disease-causing.

  In their paper, Varki, Sadowski, and Pfender et al. present the case of an eight-month-old male patie...

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  We found this paper to be immensely informative while researching junctional epidermolysis bullosa (JEB) for a particular clinical case, which is described below. During the course of testing for this particular case we found evidence suggesting that that the D982G mutation in LAMB3 may not be disease-causing.

  In their paper, Varki, Sadowski, and Pfender et al. present the case of an eight-month-old male patient who presented with mild blistering of the legs and feet at birth but who exhibited no further blistering. Mutation analysis for this boy reportedly revealed two LAMB3 missense mutations, R366W and D982G. It is not noted if phase of these mutations is known. The author suggested that the abnormal proteins arising from these alleles are able to function in the postnatal period, thus leading to spontaneous amelioration of the phenotype after birth.

  Here we present the case of an unaffected parent of a child affected with Herlitz-JEB (H-JEB) who himself is a compound heterozygote for two LAMB3 mutations, D982G and 31dupC.

  In our case, the second child born to a non-consanguineous Caucasian couple with no family history of JEB was noted to have open sores soon after birth. He was diagnosed with H-JEB based on the results of skin biopsy, and he died at five weeks of age. Molecular genetic testing identified two LAMB3 premature termination mutations, 31dupC (paternally inherited) and R635X (maternally inherited). His unaffected father was also found to carry the D982G mutation.

  The 31insC and R635X mutations in LAMB3 have been described in multiple individuals with H-JEB. To the best of our knowledge, the D982G missense mutation in LAMB3 has been described only in this paper. Our finding of this same missense mutation in trans with a more severe LAMB3 mutation in a reportedly completely unaffected individual argues against D982G being a disease-causing mutation. In addition, this mutation is predicted to be benign by Polyphen-2.

  The findings in our case argue against D982G being a disease-causing mutation, as had been suggested in this paper. However, the possibility of reduced penetrance cannot be excluded at this time.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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