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Clinical features of three girls with mosaic genome‐wide paternal uniparental isodisomy
Author(s) -
Kalish Jennifer M.,
Conlin Laura K.,
Bhatti Tricia R.,
Dubbs Holly A.,
Harris Mary Catherine,
Izumi Kosuke,
MostoufiMoab Sogol,
Mulchandani Surabhi,
Saitta Sulagna,
States Lisa J.,
Swarr Daniel T.,
Wilkens Alisha B.,
Zackai Elaine H.,
Zelley Kristin,
Bartolomei Marisa S.,
Nichols Kim E.,
Palladino Andrew A.,
Spinner Nancy B.,
Deardorff Matthew A.
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36045
Subject(s) - mosaic , uniparental disomy , genetics , biology , genome , computational biology , chromosome , history , karyotype , gene , archaeology
Here we describe three subjects with mosaic genome‐wide paternal uniparental isodisomy (GWpUPD) each of whom presented initially with overgrowth, hemihyperplasia (HH), and hyperinsulinism (HI). Due to the severity of findings and the presence of additional features, SNP array testing was performed, which demonstrated mosaic GWpUPD. Comparing these individuals to 10 other live‐born subjects reported in the literature, the predominant phenotype is that of pUPD11 and notable for a very high incidence of tumor development. Our subjects developed non‐metastatic tumors of the adrenal gland, kidney, and/or liver. All three subjects had pancreatic hyperplasia resulting in HI. Notably, our subjects to date display minimal features of other diseases associated with paternal UPD loci. Both children who survived the neonatal period have displayed near‐normal cognitive development, likely due to a favorable tissue distribution of the mosaicism. To understand the range of UPD mosaicism levels, we studied multiple tissues using SNP array analysis and detected levels of 5–95%, roughly correlating with the extent of tissue involvement. Given the rapidity of tumor growth and the difficulty distinguishing malignant and benign tumors in these GWpUPD subjects, we have utilized increased frequency of ultrasound (US) and alpha‐fetoprotein (AFP) screening in the first years of life. Because of a later age of onset of additional tumors, continued tumor surveillance into adolescence may need to be considered in these rare patients. © 2013 Wiley Periodicals, Inc.