Entry - #259440 - OSTEOGENESIS IMPERFECTA, TYPE IX; OI9 - OMIM
# 259440

OSTEOGENESIS IMPERFECTA, TYPE IX; OI9


Alternative titles; symbols

OI, TYPE IX


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
15q22.31 Osteogenesis imperfecta, type IX 259440 AR 3 PPIB 123841
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
GROWTH
Height
- Short limb dwarfism
HEAD & NECK
Eyes
- White to gray sclerae
SKELETAL
- Numerous multiple fractures present at birth
Spine
- Scoliosis
- Kyphosis
Limbs
- Bowing of limbs due to multiple fractures
MOLECULAR BASIS
- Caused by mutation in the peptidyl-prolyl isomerase B gene (PPIB, 123841.0001)
Osteogenesis imperfecta - PS166200 - 26 Entries
Location Phenotype Inheritance Phenotype
mapping key
Phenotype
MIM number
Gene/Locus Gene/Locus
MIM number
1p34.2 Osteogenesis imperfecta, type VIII AR 3 610915 P3H1 610339
3p22.3 Osteogenesis imperfecta, type VII AR 3 610682 CRTAP 605497
5q33.1 Osteogenesis imperfecta, type XVII AR 3 616507 SPARC 182120
6q14.1 Osteogenesis imperfecta, type XVIII AR 3 617952 TENT5A 611357
7p22.1 Osteogenesis imperfecta, type XXI AR 3 619131 KDELR2 609024
7q21.3 Osteogenesis imperfecta, type IV AD 3 166220 COL1A2 120160
7q21.3 Osteogenesis imperfecta, type II AD 3 166210 COL1A2 120160
7q21.3 Osteogenesis imperfecta, type III AD 3 259420 COL1A2 120160
8p21.3 Osteogenesis imperfecta, type XIII AR 3 614856 BMP1 112264
9q31.2 Osteogenesis imperfecta, type XIV AR 3 615066 TMEM38B 611236
11p15.5 Osteogenesis imperfecta, type V AD 3 610967 IFITM5 614757
11p11.2 Osteogenesis imperfecta, type XVI AR 3 616229 CREB3L1 616215
11q13.5 Osteogenesis imperfecta, type X AR 3 613848 SERPINH1 600943
11q23.3 Osteogenesis imperfecta, type XXIII AR 3 620639 PHLDB1 612834
12q13.12 Osteogenesis imperfecta, type XV AR 3 615220 WNT1 164820
12q13.13 Osteogenesis imperfecta, type XII AR 3 613849 SP7 606633
15q22.31 Osteogenesis imperfecta, type IX AR 3 259440 PPIB 123841
15q25.1 Osteogenesis imperfecta, type XX AR 3 618644 MESD 607783
17p13.3 Osteogenesis imperfecta, type VI AR 3 613982 SERPINF1 172860
17q21.2 Osteogenesis imperfecta, type XI AR 3 610968 FKBP10 607063
17q21.33 Osteogenesis imperfecta, type II AD 3 166210 COL1A1 120150
17q21.33 Osteogenesis imperfecta, type IV AD 3 166220 COL1A1 120150
17q21.33 Osteogenesis imperfecta, type I AD 3 166200 COL1A1 120150
17q21.33 Osteogenesis imperfecta, type III AD 3 259420 COL1A1 120150
22q13.2 Osteogenesis imperfecta, type XXII AR 3 619795 CCDC134 618788
Xp22.12 Osteogenesis imperfecta, type XIX XLR 3 301014 MBTPS2 300294

TEXT

A number sign (#) is used with this entry because of evidence that osteogenesis imperfecta type IX (OI9) is caused by homozygous or compound heterozygous mutation in the PPIB gene (123841) on chromosome 15q22.


Description

Osteogenesis imperfecta (OI) is a connective tissue disorder characterized clinically by bone fragility and increased susceptibility to fractures. Osteogenesis imperfecta type IX (OI9) is a severe autosomal recessive form of the disorder (summary by van Dijk et al., 2009).


Clinical Features

In an inbred Irish Traveller family, Williams et al. (1989) described severe Sillence type II/III (166210/259420) osteogenesis imperfecta in 3 consecutively born children with first-cousin parents. Three other children were unaffected. There had been other infants in the kindred with lethal OI. The first sib, a male, died at age 6 weeks. The second, a girl, was living at age 7 years and attended a normal school with the aid of an electric cart. The third was diagnosed by ultrasound, and pregnancy was terminated at 30 weeks' gestation. The lumbar spine of the mother was interpreted as showing early osteoporosis; the age of the parents was not given. Studies in the children showed overhydroxylation of type I collagen components over the entire length of the collagen and procollagen triple helix, suggesting overmodification of type I collagen. Linkage studies excluded both the COL1A1 (120150) and the COL1A2 (120160) genes as the site of the mutation in this disorder (Daw et al., 1988).

Van Dijk et al. (2009) studied 2 fetuses with osteogenesis imperfecta from a nonconsanguineous northern European family; radiographs and autopsy at 16 weeks' and 22 weeks' gestation, respectively, showed absence of rib fractures with shortened, bowed, and fractured long bones without evidence of rhizomelia, consistent with a diagnosis of Sillence OI type II. Weight and head circumference were normal for gestational age, and no other abnormalities were noted. Bone histology confirmed the diagnosis of OI, and overmodification of collagen type I in fibroblasts was evident on electrophoresis. Van Dijk et al. (2009) also studied 2 sibs with OI from a consanguineous Pakistani family, the older of whom was born with multiple long-bone fractures and had a large head with large anterior fontanel and gray-colored sclerae, flexed and abducted hips, short bowed femurs with anterior bowing of the tibiae, and joint hypermobility, especially of the finger and hip joints, consistent with a diagnosis of Sillence OI type III. There was no evidence of dentinogenesis imperfecta. The older sib, who had never walked, used a wheelchair at age 8 years and had kyphoscoliosis of the thoracic and lumbar spine, with a height at the 50th percentile for a 17-month-old child.

Barnes et al. (2010) studied a 4-year-old girl and her 12-year-old brother, born of consanguineous Senegalese parents, who had moderately severe osteogenesis imperfecta. The affected sibs did not have rhizomelia or severe deformity of the long bones, and their skin was normal in appearance and extensibility. Although they had moderate axial growth deficiency, their hand length and segmental proportions were appropriate for their age. Both children had white sclerae and normal dentition. The brother, whose osteogenesis imperfecta was milder than that of his sister, also had sickle cell disease.

Pyott et al. (2011) identified mutations in the PPIB gene in 3 families with OI9; one family had a lethal OI type II phenotype, another had a severe OI type III phenotype, and the last had a moderately severe deforming OI type III/IV phenotype.


Inheritance

The transmission pattern of OI9 in the families reported by van Dijk et al. (2009) was consistent with autosomal recessive inheritance.


Molecular Genetics

In 4 patients from 2 unrelated families with severe osteogenesis imperfecta, van Dijk et al. (2009) analyzed the PPIB gene and identified homozygosity for a frameshift (123841.0001) and a nonsense (123841.0002) mutation, respectively.

In a sister and brother who had moderately severe osteogenesis imperfecta without rhizomelia, who were born of consanguineous Senegalese parents, Barnes et al. (2010) identified homozygosity for a missense mutation in the PPIB gene (123841.0003). The proband had normal collagen folding and normal prolyl 3-hydroxylation, suggesting that CYPB is not the exclusive peptidyl-prolyl cis-trans isomerase that catalyzes the rate-limiting step in collagen folding.

In a Palestinian pedigree segregating moderate and lethal forms of OI, Barnes et al. (2012) identified a homozygous indel mutation in the FKBP10 gene (607063.0009) in a proband from one branch of the family with OI type 11 (610968), and a homozygous deletion in the PPIB gene (123841.0004) in a proband from another branch of the family with OI type IX.

In 2 sibs, born to nonconsanguineous parents, with a lethal form of OI type IX, Pyott et al. (2011) identified compound heterozygous mutations in the PPIB gene: a maternally inherited deletion (123841.0005) and a paternally inherited missense mutation (123841.0006).


See Also:

REFERENCES

  1. Barnes, A. M., Cabral, W. A., Weis, M., Makareeva, E., Mertz, E. L., Leikin, S., Eyre, D., Trujillo, C., Marini, J. C. Absence of FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished collagen cross-linking and reduced collagen deposition in extracellular matrix. Hum. Mutat. 33: 1589-1598, 2012. [PubMed: 22718341, images, related citations] [Full Text]

  2. Barnes, A. M., Carter, E. M., Cabral, W. A., Weis, M., Chang, W., Makareeva, E., Leikin, S., Rotimi, C. N., Eyre, D. R., Raggio, C. L., Marini, J. C. Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding. New Eng. J. Med. 362: 521-528, 2010. [PubMed: 20089953, images, related citations] [Full Text]

  3. Daw, S., Nicholls, A. C., Williams, M., Sykes, B., Pope, F. M. Autosomal recessive osteogenesis imperfecta: excess post translational modification of collagen not linked to either COL1A1 or COL1A2. (Abstract) J. Med. Genet. 25: 275 only, 1988.

  4. Pyott, S. M., Schwarze, U., Christiansen, H. E., Pepin, M. G., Leistritz, D. F., Dineen, R., Harris, C., Burton, B. K., Angle, B., Kim, K., Sussman, M. D., Weis, M. A., Eyre, D. R., Russell, D. W., McCarthy, K. J., Steiner, R. D., Byers, P. H. Mutations in PPIB (cyclophilin B) delay type I procollagen chain association and result in perinatal lethal to moderate osteogenesis imperfecta phenotypes. Hum. Molec. Genet. 20: 1595-1609, 2011. [PubMed: 21282188, images, related citations] [Full Text]

  5. Sillence, D. O., Senn, A., Danks, D. M. Genetic heterogeneity in osteogenesis imperfecta. J. Med. Genet. 16: 101-116, 1979. [PubMed: 458828, related citations] [Full Text]

  6. van Dijk, F. S., Nesbitt, I. M., Zwikstra, E. H., Nikkels, P. G. J., Piersma, S. R., Fratantoni, S. A., Jimenez, C. R., Huizer, M., Morsman, A. C., Cobben, J. M., van Roij, M. H. H., Elting, M. W., and 9 others. PPIB mutations cause severe osteogenesis imperfecta. Am. J. Hum. Genet. 85: 521-527, 2009. [PubMed: 19781681, images, related citations] [Full Text]

  7. Williams, E. M., Nicholls, A. C., Daw, S. C. M., Mitchell, N., Levin, L. S., Green, B., MacKenzie, J., Evans, D.-R., Chudleigh, P. A., Pope, F. M. Phenotypical features of an unique Irish family with severe autosomal recessive osteogenesis imperfecta. Clin. Genet. 35: 181-190, 1989. [PubMed: 2650933, related citations] [Full Text]


Carol A. Bocchini - updated : 12/07/2015
Nara Sobreira - updated : 3/29/2013
Marla J. F. O'Neill - updated : 6/1/2010
Marla J. F. O'Neill - updated : 5/24/2010
Creation Date:
Victor A. McKusick : 3/21/1989
carol : 12/12/2023
carol : 12/07/2015
carol : 12/7/2015
carol : 3/29/2013
carol : 11/14/2011
carol : 10/6/2011
wwang : 6/1/2010
terry : 6/1/2010
carol : 5/24/2010
carol : 10/22/2009
mimadm : 3/11/1994
supermim : 3/17/1992
supermim : 3/20/1990
ddp : 10/27/1989
root : 3/21/1989

# 259440

OSTEOGENESIS IMPERFECTA, TYPE IX; OI9


Alternative titles; symbols

OI, TYPE IX


ORPHA: 216804, 216812, 216820, 666;   DO: 0110349;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
15q22.31 Osteogenesis imperfecta, type IX 259440 Autosomal recessive 3 PPIB 123841

TEXT

A number sign (#) is used with this entry because of evidence that osteogenesis imperfecta type IX (OI9) is caused by homozygous or compound heterozygous mutation in the PPIB gene (123841) on chromosome 15q22.


Description

Osteogenesis imperfecta (OI) is a connective tissue disorder characterized clinically by bone fragility and increased susceptibility to fractures. Osteogenesis imperfecta type IX (OI9) is a severe autosomal recessive form of the disorder (summary by van Dijk et al., 2009).


Clinical Features

In an inbred Irish Traveller family, Williams et al. (1989) described severe Sillence type II/III (166210/259420) osteogenesis imperfecta in 3 consecutively born children with first-cousin parents. Three other children were unaffected. There had been other infants in the kindred with lethal OI. The first sib, a male, died at age 6 weeks. The second, a girl, was living at age 7 years and attended a normal school with the aid of an electric cart. The third was diagnosed by ultrasound, and pregnancy was terminated at 30 weeks' gestation. The lumbar spine of the mother was interpreted as showing early osteoporosis; the age of the parents was not given. Studies in the children showed overhydroxylation of type I collagen components over the entire length of the collagen and procollagen triple helix, suggesting overmodification of type I collagen. Linkage studies excluded both the COL1A1 (120150) and the COL1A2 (120160) genes as the site of the mutation in this disorder (Daw et al., 1988).

Van Dijk et al. (2009) studied 2 fetuses with osteogenesis imperfecta from a nonconsanguineous northern European family; radiographs and autopsy at 16 weeks' and 22 weeks' gestation, respectively, showed absence of rib fractures with shortened, bowed, and fractured long bones without evidence of rhizomelia, consistent with a diagnosis of Sillence OI type II. Weight and head circumference were normal for gestational age, and no other abnormalities were noted. Bone histology confirmed the diagnosis of OI, and overmodification of collagen type I in fibroblasts was evident on electrophoresis. Van Dijk et al. (2009) also studied 2 sibs with OI from a consanguineous Pakistani family, the older of whom was born with multiple long-bone fractures and had a large head with large anterior fontanel and gray-colored sclerae, flexed and abducted hips, short bowed femurs with anterior bowing of the tibiae, and joint hypermobility, especially of the finger and hip joints, consistent with a diagnosis of Sillence OI type III. There was no evidence of dentinogenesis imperfecta. The older sib, who had never walked, used a wheelchair at age 8 years and had kyphoscoliosis of the thoracic and lumbar spine, with a height at the 50th percentile for a 17-month-old child.

Barnes et al. (2010) studied a 4-year-old girl and her 12-year-old brother, born of consanguineous Senegalese parents, who had moderately severe osteogenesis imperfecta. The affected sibs did not have rhizomelia or severe deformity of the long bones, and their skin was normal in appearance and extensibility. Although they had moderate axial growth deficiency, their hand length and segmental proportions were appropriate for their age. Both children had white sclerae and normal dentition. The brother, whose osteogenesis imperfecta was milder than that of his sister, also had sickle cell disease.

Pyott et al. (2011) identified mutations in the PPIB gene in 3 families with OI9; one family had a lethal OI type II phenotype, another had a severe OI type III phenotype, and the last had a moderately severe deforming OI type III/IV phenotype.


Inheritance

The transmission pattern of OI9 in the families reported by van Dijk et al. (2009) was consistent with autosomal recessive inheritance.


Molecular Genetics

In 4 patients from 2 unrelated families with severe osteogenesis imperfecta, van Dijk et al. (2009) analyzed the PPIB gene and identified homozygosity for a frameshift (123841.0001) and a nonsense (123841.0002) mutation, respectively.

In a sister and brother who had moderately severe osteogenesis imperfecta without rhizomelia, who were born of consanguineous Senegalese parents, Barnes et al. (2010) identified homozygosity for a missense mutation in the PPIB gene (123841.0003). The proband had normal collagen folding and normal prolyl 3-hydroxylation, suggesting that CYPB is not the exclusive peptidyl-prolyl cis-trans isomerase that catalyzes the rate-limiting step in collagen folding.

In a Palestinian pedigree segregating moderate and lethal forms of OI, Barnes et al. (2012) identified a homozygous indel mutation in the FKBP10 gene (607063.0009) in a proband from one branch of the family with OI type 11 (610968), and a homozygous deletion in the PPIB gene (123841.0004) in a proband from another branch of the family with OI type IX.

In 2 sibs, born to nonconsanguineous parents, with a lethal form of OI type IX, Pyott et al. (2011) identified compound heterozygous mutations in the PPIB gene: a maternally inherited deletion (123841.0005) and a paternally inherited missense mutation (123841.0006).


See Also:

Sillence et al. (1979)

REFERENCES

  1. Barnes, A. M., Cabral, W. A., Weis, M., Makareeva, E., Mertz, E. L., Leikin, S., Eyre, D., Trujillo, C., Marini, J. C. Absence of FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished collagen cross-linking and reduced collagen deposition in extracellular matrix. Hum. Mutat. 33: 1589-1598, 2012. [PubMed: 22718341] [Full Text: https://doi.org/10.1002/humu.22139]

  2. Barnes, A. M., Carter, E. M., Cabral, W. A., Weis, M., Chang, W., Makareeva, E., Leikin, S., Rotimi, C. N., Eyre, D. R., Raggio, C. L., Marini, J. C. Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding. New Eng. J. Med. 362: 521-528, 2010. [PubMed: 20089953] [Full Text: https://doi.org/10.1056/NEJMoa0907705]

  3. Daw, S., Nicholls, A. C., Williams, M., Sykes, B., Pope, F. M. Autosomal recessive osteogenesis imperfecta: excess post translational modification of collagen not linked to either COL1A1 or COL1A2. (Abstract) J. Med. Genet. 25: 275 only, 1988.

  4. Pyott, S. M., Schwarze, U., Christiansen, H. E., Pepin, M. G., Leistritz, D. F., Dineen, R., Harris, C., Burton, B. K., Angle, B., Kim, K., Sussman, M. D., Weis, M. A., Eyre, D. R., Russell, D. W., McCarthy, K. J., Steiner, R. D., Byers, P. H. Mutations in PPIB (cyclophilin B) delay type I procollagen chain association and result in perinatal lethal to moderate osteogenesis imperfecta phenotypes. Hum. Molec. Genet. 20: 1595-1609, 2011. [PubMed: 21282188] [Full Text: https://doi.org/10.1093/hmg/ddr037]

  5. Sillence, D. O., Senn, A., Danks, D. M. Genetic heterogeneity in osteogenesis imperfecta. J. Med. Genet. 16: 101-116, 1979. [PubMed: 458828] [Full Text: https://doi.org/10.1136/jmg.16.2.101]

  6. van Dijk, F. S., Nesbitt, I. M., Zwikstra, E. H., Nikkels, P. G. J., Piersma, S. R., Fratantoni, S. A., Jimenez, C. R., Huizer, M., Morsman, A. C., Cobben, J. M., van Roij, M. H. H., Elting, M. W., and 9 others. PPIB mutations cause severe osteogenesis imperfecta. Am. J. Hum. Genet. 85: 521-527, 2009. [PubMed: 19781681] [Full Text: https://doi.org/10.1016/j.ajhg.2009.09.001]

  7. Williams, E. M., Nicholls, A. C., Daw, S. C. M., Mitchell, N., Levin, L. S., Green, B., MacKenzie, J., Evans, D.-R., Chudleigh, P. A., Pope, F. M. Phenotypical features of an unique Irish family with severe autosomal recessive osteogenesis imperfecta. Clin. Genet. 35: 181-190, 1989. [PubMed: 2650933] [Full Text: https://doi.org/10.1111/j.1399-0004.1989.tb02926.x]


Contributors:
Carol A. Bocchini - updated : 12/07/2015
Nara Sobreira - updated : 3/29/2013
Marla J. F. O'Neill - updated : 6/1/2010
Marla J. F. O'Neill - updated : 5/24/2010

Creation Date:
Victor A. McKusick : 3/21/1989

Edit History:
carol : 12/12/2023
carol : 12/07/2015
carol : 12/7/2015
carol : 3/29/2013
carol : 11/14/2011
carol : 10/6/2011
wwang : 6/1/2010
terry : 6/1/2010
carol : 5/24/2010
carol : 10/22/2009
mimadm : 3/11/1994
supermim : 3/17/1992
supermim : 3/20/1990
ddp : 10/27/1989
root : 3/21/1989