Novel mutation in the carboxyl-terminal propeptide of the procollagen α1(I) chain in a girl with prenatal cortical hyperostosis and multiple fractures

K. M. Roetzer, F. Laccone, A. Krebs, F. Grill, S. Robins, F. Varga, K. Klaushofer, A. Al Kaissi

Research output: Contribution to journalArticle

Abstract

Mutations in the gene encoding the procollagen a1(I) chain (COL1A1) usually cause the autosomal-dominant bone dysplasia osteogenesis imperfecta (OI), which is characterized by the occurrence of fractures without adequate trauma. In addition, some mutations are known to result in Ehlers–Danlos-Syndrome (EDS), and one mutation is associated with infantile cortical hyperostosis (Caffey-disease).

We report on a girl of non-consanguineous parents, who exhibited cortical hyperostosis as well as multiple fractures at birth. Sequence analysis revealed a novel and probably de novo missense mutation in exon 50 of the COL1A1-gene, which encodes a part of the carboxyl-terminal propeptide of the procollagen a1(I) chain. Mutations in this location are very rare and can cause a wide range of severities in OI, but no case of cortical hyperostosis has been reported to date. In addition, we performed biochemical analyses of serum and urine samples, allele-ancestry analysis, as well as an in silico protein prediction, which showed significant structural changes around the propeptide site involved in protein chain association.

Interestingly, the healthy father of our patient also showed hyperostosis, mainly at the mandible, although the mutation could not be detected in his peripheral blood cells. Two possible explanations for these observations are discussed; firstly, that the presence of fractures and hyperostosis are coincidental with the mutation associated only with the fractures and, secondly, that the father is carrier of a somatic mosaic (including the gonads) of the mutation which we were unable to detect.
Original languageEnglish
Pages (from-to)S81
Number of pages1
JournalBone
Volume45
Issue numberSuppl. 2
Early online date24 Jun 2009
DOIs
Publication statusPublished - Jul 2009

Cite this

Novel mutation in the carboxyl-terminal propeptide of the procollagen α1(I) chain in a girl with prenatal cortical hyperostosis and multiple fractures. / Roetzer, K. M.; Laccone, F.; Krebs, A.; Grill, F.; Robins, S.; Varga, F.; Klaushofer, K.; Al Kaissi, A.

In: Bone, Vol. 45, No. Suppl. 2, 07.2009, p. S81.

Research output: Contribution to journalArticle

Roetzer, KM, Laccone, F, Krebs, A, Grill, F, Robins, S, Varga, F, Klaushofer, K & Al Kaissi, A 2009, 'Novel mutation in the carboxyl-terminal propeptide of the procollagen α1(I) chain in a girl with prenatal cortical hyperostosis and multiple fractures', Bone, vol. 45, no. Suppl. 2, pp. S81. https://doi.org/10.1016/j.bone.2009.04.106
Roetzer, K. M. ; Laccone, F. ; Krebs, A. ; Grill, F. ; Robins, S. ; Varga, F. ; Klaushofer, K. ; Al Kaissi, A. / Novel mutation in the carboxyl-terminal propeptide of the procollagen α1(I) chain in a girl with prenatal cortical hyperostosis and multiple fractures. In: Bone. 2009 ; Vol. 45, No. Suppl. 2. pp. S81.
@article{3150718434dd4ed296c90e8e8887bac4,
title = "Novel mutation in the carboxyl-terminal propeptide of the procollagen α1(I) chain in a girl with prenatal cortical hyperostosis and multiple fractures",
abstract = "Mutations in the gene encoding the procollagen a1(I) chain (COL1A1) usually cause the autosomal-dominant bone dysplasia osteogenesis imperfecta (OI), which is characterized by the occurrence of fractures without adequate trauma. In addition, some mutations are known to result in Ehlers–Danlos-Syndrome (EDS), and one mutation is associated with infantile cortical hyperostosis (Caffey-disease).We report on a girl of non-consanguineous parents, who exhibited cortical hyperostosis as well as multiple fractures at birth. Sequence analysis revealed a novel and probably de novo missense mutation in exon 50 of the COL1A1-gene, which encodes a part of the carboxyl-terminal propeptide of the procollagen a1(I) chain. Mutations in this location are very rare and can cause a wide range of severities in OI, but no case of cortical hyperostosis has been reported to date. In addition, we performed biochemical analyses of serum and urine samples, allele-ancestry analysis, as well as an in silico protein prediction, which showed significant structural changes around the propeptide site involved in protein chain association.Interestingly, the healthy father of our patient also showed hyperostosis, mainly at the mandible, although the mutation could not be detected in his peripheral blood cells. Two possible explanations for these observations are discussed; firstly, that the presence of fractures and hyperostosis are coincidental with the mutation associated only with the fractures and, secondly, that the father is carrier of a somatic mosaic (including the gonads) of the mutation which we were unable to detect.",
author = "Roetzer, {K. M.} and F. Laccone and A. Krebs and F. Grill and S. Robins and F. Varga and K. Klaushofer and {Al Kaissi}, A.",
year = "2009",
month = "7",
doi = "10.1016/j.bone.2009.04.106",
language = "English",
volume = "45",
pages = "S81",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "Suppl. 2",

}

TY - JOUR

T1 - Novel mutation in the carboxyl-terminal propeptide of the procollagen α1(I) chain in a girl with prenatal cortical hyperostosis and multiple fractures

AU - Roetzer, K. M.

AU - Laccone, F.

AU - Krebs, A.

AU - Grill, F.

AU - Robins, S.

AU - Varga, F.

AU - Klaushofer, K.

AU - Al Kaissi, A.

PY - 2009/7

Y1 - 2009/7

N2 - Mutations in the gene encoding the procollagen a1(I) chain (COL1A1) usually cause the autosomal-dominant bone dysplasia osteogenesis imperfecta (OI), which is characterized by the occurrence of fractures without adequate trauma. In addition, some mutations are known to result in Ehlers–Danlos-Syndrome (EDS), and one mutation is associated with infantile cortical hyperostosis (Caffey-disease).We report on a girl of non-consanguineous parents, who exhibited cortical hyperostosis as well as multiple fractures at birth. Sequence analysis revealed a novel and probably de novo missense mutation in exon 50 of the COL1A1-gene, which encodes a part of the carboxyl-terminal propeptide of the procollagen a1(I) chain. Mutations in this location are very rare and can cause a wide range of severities in OI, but no case of cortical hyperostosis has been reported to date. In addition, we performed biochemical analyses of serum and urine samples, allele-ancestry analysis, as well as an in silico protein prediction, which showed significant structural changes around the propeptide site involved in protein chain association.Interestingly, the healthy father of our patient also showed hyperostosis, mainly at the mandible, although the mutation could not be detected in his peripheral blood cells. Two possible explanations for these observations are discussed; firstly, that the presence of fractures and hyperostosis are coincidental with the mutation associated only with the fractures and, secondly, that the father is carrier of a somatic mosaic (including the gonads) of the mutation which we were unable to detect.

AB - Mutations in the gene encoding the procollagen a1(I) chain (COL1A1) usually cause the autosomal-dominant bone dysplasia osteogenesis imperfecta (OI), which is characterized by the occurrence of fractures without adequate trauma. In addition, some mutations are known to result in Ehlers–Danlos-Syndrome (EDS), and one mutation is associated with infantile cortical hyperostosis (Caffey-disease).We report on a girl of non-consanguineous parents, who exhibited cortical hyperostosis as well as multiple fractures at birth. Sequence analysis revealed a novel and probably de novo missense mutation in exon 50 of the COL1A1-gene, which encodes a part of the carboxyl-terminal propeptide of the procollagen a1(I) chain. Mutations in this location are very rare and can cause a wide range of severities in OI, but no case of cortical hyperostosis has been reported to date. In addition, we performed biochemical analyses of serum and urine samples, allele-ancestry analysis, as well as an in silico protein prediction, which showed significant structural changes around the propeptide site involved in protein chain association.Interestingly, the healthy father of our patient also showed hyperostosis, mainly at the mandible, although the mutation could not be detected in his peripheral blood cells. Two possible explanations for these observations are discussed; firstly, that the presence of fractures and hyperostosis are coincidental with the mutation associated only with the fractures and, secondly, that the father is carrier of a somatic mosaic (including the gonads) of the mutation which we were unable to detect.

U2 - 10.1016/j.bone.2009.04.106

DO - 10.1016/j.bone.2009.04.106

M3 - Article

VL - 45

SP - S81

JO - Bone

JF - Bone

SN - 8756-3282

IS - Suppl. 2

ER -