Article (Scientific journals)
Genomic deletions of OFD1 account for 23% of oral-facial-digital type 1 syndrome after negative DNA sequencing.
Thauvin-Robinet, Christel; Franco, Brunella; Saugier-Veber, Pascale et al.
2008In Human Mutation, 30 (2), p. 320-9
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Keywords :
Female; Genome, Human/genetics; Humans; Orofaciodigital Syndromes/genetics; Polymerase Chain Reaction; Proteins/genetics; Sequence Analysis, DNA; Sequence Deletion
Abstract :
[en] Oral-facial-digital type I syndrome (OFDI) is characterised by an X-linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, dental and distal abnormalities, polycystic kidney disease and central nervous system malformations. Considerable allelic heterogeneity has been reported within the OFD1 gene, but DNA bi-directional sequencing of the exons and intron-exon boundaries of the OFD1 gene remains negative in more than 20% of cases. We hypothesized that genomic rearrangements could account for the majority of the remaining undiagnosed cases. Thus, we took advantage of two independent available series of patients with OFDI syndrome and negative DNA bi-directional sequencing of the exons and intron-exon boundaries of the OFD1 gene from two different European labs: 13/36 cases from the French lab; 13/95 from the Italian lab. All patients were screened by a semiquantitative fluorescent multiplex method (QFMPSF) and relative quantification by real-time PCR (qPCR). Six OFD1 genomic deletions (exon 5, exons 1-8, exons 1-14, exons 10-11, exons 13-23 and exon 17) were identified, accounting for 5% of OFDI patients and for 23% of patients with negative mutation screening by DNA sequencing. The association of DNA direct sequencing, QFMPSF and qPCR detects OFD1 alteration in up to 85% of patients with a phenotype suggestive of OFDI syndrome. Given the average percentage of large genomic rearrangements (5%), we suggest that dosage methods should be performed in addition to DNA direct sequencing analysis to exclude the involvement of the OFD1 transcript when there are genetic counselling issues.
Disciplines :
Genetics & genetic processes
Author, co-author :
Thauvin-Robinet, Christel
Franco, Brunella
Saugier-Veber, Pascale
Aral, Bernard
Gigot, Nadege
Donzel, Anne
Van Maldergem, Lionel ;  Centre Hospitalier Universitaire de Liège - CHU > Génétique
Bieth, Eric
Layet, Valerie
Mathieu, Michele
Teebi, Ahmad
Lespinasse, James
Callier, Patrick
Mugneret, Francine
Masurel-Paulet, Alice
Gautier, Elodie
Huet, Frederic
Teyssier, Jean-Raymond
Tosi, Mario
Frebourg, Thierry
Faivre, Laurence
More authors (11 more) Less
Language :
English
Title :
Genomic deletions of OFD1 account for 23% of oral-facial-digital type 1 syndrome after negative DNA sequencing.
Publication date :
2008
Journal title :
Human Mutation
ISSN :
1059-7794
eISSN :
1098-1004
Publisher :
Wiley Liss, Hoboken, United States - New Jersey
Volume :
30
Issue :
2
Pages :
E320-9
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 2008 Wiley-Liss, Inc.
Available on ORBi :
since 02 February 2010

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