Frameshift mutation in the cartilage-derived morphogenetic protein 1 (CDMP1) gene and severe acromesomelic chondrodysplasia resembling Grebe-type chondrodysplasia.
Grebe-type chondrodysplasia exhibits a severe form of limb shortening and appendicular bone dysmorphogenesis. Here we report a family with seven males and six females who inherited the disorder in an autosomal recessive fashion. While the carrier parents did not exhibit any apparent skeletal abnormalities, all affected patients had a similar phenotype with unaffected axial and craniofacial bones. Since mutations in the cartilage-derived morphogenetic protein 1 (CDMP1) gene have been reported in similar acromesomelic chondrodysplasias, we examined genomic DNA from affected and normal subjects for possible mutations in CDMP1. In affected subjects, an insertion of a C at nucleotide 297 of the coding sequence was discovered. This insertion produced a shift in the reading frame at amino acid residue 99, causing premature termination of the polypeptide six amino acids downstream. DNA samples from 41 control subjects did not show this mutation. The truncated CDMP1 protein in these subjects is predicted to cause a total loss of its signaling function. The present report confirms that CDMP1 plays an important role in the regulation of axial bone growth during development and suggests that its absence does not impair other developmental processes.
The Hospital for Sick Children, Toronto, Ontario, Canada. muhammad@genet.sickkids.on.ca
Muhammad
M
Faiyaz-Ul-Haque
Wasim
W
Ahmad
Abdul
A
Wahab
Sayedul
S
Haque
Anser C
AC
Azim
Syed H E
SH
Zaidi
Ahmad S
AS
Teebi
Mahmud
M
Ahmad
Daniel H
DH
Cohn
Teepu
T
Siddique
Lap-Chee
LC
Tsui
D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000502:physiology; D018389:Codon, Nonsense; D003241:Consanguinity; D004392:Dwarfism / Q000235:genetics*; D005260:Female; D005532:Foot Deformities, Congenital / Q000235:genetics; D005808:Genes, Recessive; D055428:Growth Differentiation Factor 5; D006228:Hand Deformities, Congenital / Q000235:genetics; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010154:Pakistan; D010375:Pedigree; D010641:Phenotype
D019485:Bone Morphogenetic Proteins; D018389:Codon, Nonsense; D055428:Growth Differentiation Factor 5