Complete COL1A1 allele deletions in osteogenesis imperfecta.
OBJECTIVE
To identify a molecular genetic cause in patients with a clinical diagnosis of osteogenesis imperfecta (OI) type I/IV.


METHODS
The authors performed multiplex ligation-dependent probe amplification analysis of the COL1A1 gene in a group of 106 index patients.


RESULTS
In four families with mild osteogenesis imperfecta and no other phenotypic abnormalities, a deletion of the complete COL1A1 gene on one allele was detected, a molecular finding that to our knowledge has not been described before, apart from a larger chromosomal deletion detected by fluorescent in situ hybridization encompassing the COL1A1 gene in a patient with mild osteogenesis imperfecta and other phenotypic abnormalities. Microarray analysis in three of the four families showed that it did not concern a founder mutation.


CONCLUSIONS
The clinical picture of complete COL1A1 allele deletions is a comparatively mild type of osteogenesis imperfecta. As such, multiplex ligation-dependent probe amplification analysis of the COL1A1 gene is a useful additional approach to defining the mutation in cases of suspected osteogenesis imperfecta type I with no detectable mutation.
Department of Clinical Genetics, VU University Medical Centre, Amsterdam, the Netherlands.
Fleur S
FS
van Dijk
Margriet
M
Huizer
Ariana
A
Kariminejad
Carlo L
CL
Marcelis
Astrid S
AS
Plomp
Paulien A
PA
Terhal
Hanne
H
Meijers-Heijboer
Marjan M
MM
Weiss
Rick R
RR
van Rijn
Jan M
JM
Cobben
Gerard
G
Pals
D000328:Adult; D000483:Alleles; D002648:Child; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D018703:Founder Effect; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D010375:Pedigree
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain