Identification of the first multi-exonic WDR72 deletion in isolated amelogenesis imperfecta, and generation of a WDR72-specific copy number screening tool.
Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous disorder of tooth development which is due to aberrant deposition or composition of enamel. Both syndromic and isolated forms exist; they may be inherited in an X-linked, autosomal recessive, or autosomal dominant manner. WDR72 is one of ten currently known genes for recessive isolated AI; nine WDR72 mutations affecting single nucleotides have been described to date. Based on whole exome sequencing in a large consanguineous AI pedigree, we obtained evidence for presence of a multi-exonic WDR72 deletion. A home-made multiplex ligation-dependent probe amplification assay was used to confirm the aberration, to narrow its extent, and to identify heterozygous carriers. Our study extends the mutational spectrum for WDR72 to include large deletions, and supports a relevance of the previously proposed loss-of-function mechanism. It also introduces an easy-to-use and highly sensitive tool for detecting WDR72 copy number alterations.
Institute of Human Genetics, Jena University Hospital, Jena, Germany; Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany.
Julia
J
Hentschel
Institute of Medical and Human Genetics, Charité, Universitaetsmedizin Berlin, Germany.
Dana
D
Tatun
Institute of Medical and Human Genetics, Charité, Universitaetsmedizin Berlin, Germany.
Dmitri
D
Parkhomchuk
Institute of Human Genetics, Jena University Hospital, Jena, Germany.
Ingo
I
Kurth
Institute of Human Genetics, Jena University Hospital, Jena, Germany.
Bettina
B
Schimmel
Department of Preventive and Paediatric Dentistry, Jena University Hospital, Jena, Germany.
Roswitha
R
Heinrich-Weltzien
Dental Practice, Bremen, Germany.
Sabine
S
Bertzbach
Institute of Medical and Human Genetics, Charité, Universitaetsmedizin Berlin, Germany; ChariteVivantes GmbH, Berlin, Germany.
Hartmut
H
Peters
Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany. Electronic address: christian.beetz@med.uni-jena.de.
Christian
C
Beetz
D000567:Amelogenesis Imperfecta / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D003241:Consanguinity; D003743:Dental Enamel / Q000378:metabolism / Q000473:pathology; D059472:Exome; D005091:Exons; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
D011506:Proteins; C545712:WDR72 protein, human
Amelogenesis imperfecta; Copy number variant; Genomic deletion; Multiplex ligation-dependent probe amplification; WDR72