Paternal Germ Cell Mosaicism in Autosomal Dominant Pachyonychia Congenita | Congenital Defects | JAMA Dermatology | JAMA Network
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Sep 2011

Paternal Germ Cell Mosaicism in Autosomal Dominant Pachyonychia Congenita

Author Affiliations

Author Affiliations: Department of Dermatology, University of Utah, Salt Lake City (Drs Pho, Eliason, and Leachman); Epithelial Genetics Group, Division of Molecular Medicine, Colleges of Life Sciences and Medicine, Dentistry, & Nursing, University of Dundee, Dundee, Scotland (Drs Smith and McLean); GeneDx, Gaithersburg, Maryland (Drs Konecki and Bale); and Department of Dermatology, Johns Hopkins University, Baltimore, Maryland (Dr Cohen).

Arch Dermatol. 2011;147(9):1077-1080. doi:10.1001/archdermatol.2011.124

Background Pachyonychia congenita (PC) is a genodermatosis caused by mutations in 1 of 4 known keratin genes, including KRT6A, KRT6B, KRT16, or KRT17. The most common mode of inheritance is autosomal dominant. Families with an affected parent are routinely counseled about the 50% transmission risk to each offspring. In some cases, families with a rare disorder like PC can initially present with an affected child while both parents are unaffected. This is usually the result of a spontaneous in utero mutation, and the risk of subsequent offspring being affected with the same condition is negligible (but may be increased above the general population's risk, although the exact risk is not currently known for PC).

Observations We discuss a case of 2 affected children born to unaffected parents. We performed mutational analyses of all 4 individuals in the family on DNA extracted from lymphocytes. Owing to the unusual presentation of 2 affected siblings, we also extracted DNA from the father's sperm cells for keratin gene mutational analysis. We describe the first case, to our knowledge, of germ cell mosaicism in PC.

Conclusion Counseling of unaffected parents with a first child diagnosed as having PC should entail a discussion of the possibility of germ cell mosaicism contributing to an increased risk of having subsequent affected children.