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Novel ANKH mutation in a patient with sporadic craniometaphyseal dysplasia
Author(s) -
Zajac Allison,
Baek SeungHak,
Salhab Imad,
Radecki Melissa A.,
Kim Sukwha,
Hakonarson Hakon,
Nah HyunDuck
Publication year - 2010
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.33317
Subject(s) - mutation , mutant , exon , cytoplasm , microbiology and biotechnology , biology , dysplasia , mutant protein , gene , genetics
Craniometaphyseal dysplasia is caused by mutations in ANKH (ankylosis, progressive homolog [mouse]) in the majority of cases, and all of the reported mutations are single amino acid changes. Genomic DNA from an affected patient, his biological parents, and a sibling was amplified and ANKH was sequenced. The affected patient had a complex heterozygous mutation in exon 7 (c.936T > C, c.938C > G, c.942_953delTGGTTGACGGAA), predicting p.Try290Gln and p.Trp292_Glu295del. We studied the effect of the predicted mutation on the subcellular distribution of ANKH protein. Immunofluorescent labeling of COS‐7 cells transduced with normal or mutant Ank ( murine progressive ankylosis ), showed that normal Ank localized to both the plasma membrane and cytoplasm, whereas mutant Ank was detected only in the cytoplasmic compartment. We propose that this craniometaphyseal dysplasia mutation causes a loss of ANKH protein expression and activity in the plasma membrane as a result of aberrant intracellular protein trafficking. © 2010 Wiley‐Liss, Inc.