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Novel missense mutations and a 288‐bp exonic insertion in PAX9 in families with autosomal dominant hypodontia
Author(s) -
Das Parimal,
Hai Mehreen,
Elcock Claire,
Leal Suzanne M.,
Brown Donald T.,
Brook Alan H.,
Patel Pragna I.
Publication year - 2002
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.10011
Subject(s) - missense mutation , genetics , hypodontia , exon , frameshift mutation , biology , locus (genetics) , intron , gene , mutation , medicine , dentistry
We describe the molecular analysis of three families with hypodontia involving primarily molar teeth and report two novel mutational mechanisms. Linkage analysis of two large families revealed that the hypodontia was linked to the PAX9 locus. These two families revealed missense mutations consisting of a glutamic acid substitution for lysine and a proline substitution for leucine within the paired domain of PAX9. A pair of identical twins affected with hypodontia in a third family demonstrated a 288‐bp insertion within exon 2 that resulted in a putative frameshift mutation and a premature stop codon. The insertion was associated with the loss of 7‐bp from exon 2. A block of 256‐bp of sequence within the insertion was completely identical to downstream sequence from the second intron of the PAX9 gene. These studies extend the spectrum of mutations in PAX9 associated with hypodontia to include heretofore undescribed categories, including missense mutations. © 2003 Wiley‐Liss, Inc.