TY - JOUR
T1 - LEOPARD syndrome with partly normal skin and sex chromosome mosaicism
AU - Writzl, Karin
AU - Hoovers, Jan
AU - Sistermans, Erik A.
AU - Hennekam, Raoul C.M.
PY - 2007/11/1
Y1 - 2007/11/1
N2 - We report on a family with LEOPARD syndrome which was molecularly proven (p.Thr468Met in PTPN11) in a father and his adult son. The father had multiple lentigines dispersed equally over his body; the son was similarly affected except for the left part of thorax, back and left arm, which were completely devoid of lentigines and only showed a few nevi. In addition, the son was found to have a mosaic karyotype, 47,XYY/46,XY, in lymphocytes. Skin biopsies from the pigmented and unpigmented forearm showed that mainly a 47,XYY karyotype was present in the pigmented skin and mainly a 46,XY karyotype in the unpigmented skin. In both fibroblast cultures the PTPN11 mutation was present, and no additional mutation could be detected. We discuss the various possible explanations for this phenotype, which include the possibility of coincidence; revertant mosaicism; silencing of a second PTPN11 mutation; gene(s) located on a sex chromosome influencing the phenotype; and epigenetic influences. We favor that the co-occurrence of a sex chromosome mosaicism and mosaicism for skin symptoms in a single patient with LEOPARD syndrome is coincidence, but that mosaicism for LEOPARD skin symptoms in itself may well be more frequent and needs additional studies. Each of the above-hypothesized mechanisms may then remain possible.
AB - We report on a family with LEOPARD syndrome which was molecularly proven (p.Thr468Met in PTPN11) in a father and his adult son. The father had multiple lentigines dispersed equally over his body; the son was similarly affected except for the left part of thorax, back and left arm, which were completely devoid of lentigines and only showed a few nevi. In addition, the son was found to have a mosaic karyotype, 47,XYY/46,XY, in lymphocytes. Skin biopsies from the pigmented and unpigmented forearm showed that mainly a 47,XYY karyotype was present in the pigmented skin and mainly a 46,XY karyotype in the unpigmented skin. In both fibroblast cultures the PTPN11 mutation was present, and no additional mutation could be detected. We discuss the various possible explanations for this phenotype, which include the possibility of coincidence; revertant mosaicism; silencing of a second PTPN11 mutation; gene(s) located on a sex chromosome influencing the phenotype; and epigenetic influences. We favor that the co-occurrence of a sex chromosome mosaicism and mosaicism for skin symptoms in a single patient with LEOPARD syndrome is coincidence, but that mosaicism for LEOPARD skin symptoms in itself may well be more frequent and needs additional studies. Each of the above-hypothesized mechanisms may then remain possible.
KW - LEOPARD syndrome
KW - Lentigines
KW - Mosaicism
KW - Revertant mosaicism
KW - Sex chromosome mosaicism
UR - http://www.scopus.com/inward/record.url?scp=35848947237&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ajmg.a.31991
DO - https://doi.org/10.1002/ajmg.a.31991
M3 - Article
C2 - 17935252
SN - 1552-4825
VL - 143
SP - 2612
EP - 2615
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 21
ER -