Entry - #610968 - OSTEOGENESIS IMPERFECTA, TYPE XI; OI11 - OMIM
# 610968

OSTEOGENESIS IMPERFECTA, TYPE XI; OI11


Alternative titles; symbols

OI, TYPE XI


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
17q21.2 Osteogenesis imperfecta, type XI 610968 AR 3 FKBP10 607063
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
GROWTH
Height
- Short stature (childhood)
- Birth length normal
Weight
- Birth weight normal
HEAD & NECK
Head
- Brachycephaly
Face
- Triangular face
Eyes
- White to faintly blue sclera
Teeth
- Dentinogenesis imperfecta (in one family)
SKELETAL
- Moderate to severe bone fragility
- Moderately deforming osteogenesis imperfecta
- Joint laxity
- Decreased bone mineral density Z score
- Osteopenia
Skull
- Wormian bones (in some patients)
Spine
- Wedge-shaped vertebrae
- Biconcave vertebrae
- Vertebral compression fractures (8/8 patients)
- Scoliosis (5/8 patients)
- Kyphoscoliosis
Pelvis
- Unilateral/bilateral coxa vara (5/8 patients)
- Protrusio acetabuli (4/8 patients)
- 'Fish-scale' pattern of lamellae
- Increased osteoid volume
- Hyperosteoidosis
Limbs
- Bulbous metaphyses (2/8 patients)
- Bowed extremities
- Long bone deformity
SKIN, NAILS, & HAIR
Skin
- Normal skin
- No easy bruisability
LABORATORY ABNORMALITIES
- Elevated serum alkaline phosphatase
MISCELLANEOUS
- Onset of fractures 4-18 months of life
- Severe ambulatory restriction
MOLECULAR BASIS
- Caused by mutation in the FK506-binding protein 10 gene (FKBP10, 607063.0001)
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 III AD 3 259420 COL1A1 120150
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
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 osteogenesis imperfecta type XI (OI11) is caused by homozygous or compound heterozygous mutation in the FKBP10 gene (607063) on chromosome 17q21.


Description

Osteogenesis imperfecta (OI) comprises a group of connective tissue disorders characterized by bone fragility and low bone mass. The disorder is clinically and genetically heterogeneous. OI type XI is an autosomal recessive form of OI (summary by Alanay et al., 2010).


Clinical Features

Alanay et al. (2010) studied 5 consanguineous families from northern Turkey in which a severe progressive deforming type of OI cosegregated with autosomal recessive epidermolysis bullosa simplex (131900), the latter resulting from a defect in keratin-14 (148066). Dentinogenesis imperfecta, a feature of OI type III (259420), was absent. The histologic features included a distorted lamellar structure and a fish scale-like pattern, along with elevated serum alkaline phosphatase. Alanay et al. (2010) also studied a Mexican family in which 3 sibs of consanguineous parents had severe progressive deforming OI.

Steinlein et al. (2011) described 3 German male sibs with a severe form of OI who were homozygous for a mutation in the FKBP10 gene (607063.0008). All 3 had dentinogenesis imperfecta and none showed contractures or webbing.


Inheritance

Alanay et al. (2010) confirmed autosomal recessive inheritance of OI type XI by the finding of homozygous mutations in the FKBP10 gene in affected members of 5 Turkish families and 1 Mexican family.


Mapping

In 5 consanguineous Turkish families segregating OI type XI and generalized epidermolysis bullosa simplex, the latter caused by mutation in the KRT14 gene, Alanay et al. (2010) determined that all affected individuals shared a 0.83-Mb region of homozygosity on chromosome 17q21.


Molecular Genetics

In affected members of 5 consanguineous Turkish families segregating autosomal recessive epidermolysis bullosa simplex (139100) and OI type XI, Alanay et al. (2010) identified homozygosity for 2 mutations: a missense mutation in the KRT14 gene (148066.0006) known to cause EB simplex and an in-frame deletion in the FKBP10 gene (607063.0001) causing OI. In 3 Mexican sibs with OI type XI, they identified homozygosity for a null mutation in the FKBP10 gene (607063.0002). Neither mutation was found in a panel of 210 alleles from ethnically matched unaffected individuals. The FKBP10 gene encodes a chaperone that participates in type I procollagen folding, and Alanay et al. (2010) determined that FKBP10 mutations affect type I procollagen secretion.

In 2 brothers with Bruck syndrome (BRKS1; 259450), Shaheen et al. (2010) identified a homozygous mutation in the FKBP10 gene (607063.0003). They suggested that their patients and the patients reported by Alanay et al. (2010) with OI may both have had Bruck syndrome and that bisphosphonate therapy may explain the less severe phenotype in their patients. In response to Shaheen et al. (2010), Alanay and Krakow (2010) noted that a wide phenotypic range of severity can result from different mutations in the same gene and suggested that the disorder caused by mutation in the FKBP10 gene be categorized as a recessive form of progressive deforming OI with or without joint contractures.

Kelley et al. (2011) sequenced the FKBP10 gene in 6 individuals from 5 families with a moderately severe OI phenotype, 4 with congenital joint contractures (Bruck syndrome; 259450) and 1 (patient 2) without contractures. The patient without contractures had a 35-bp deletion (607063.0004).

Barnes et al. (2012) identified a Palestinian pedigree with moderate and lethal forms of recessive OI caused by mutations in the FKBP10 or PPIB (123841) gene. In 1 pedigree branch, a child with moderate type XI OI was homozygous for the indel mutation in the FKBP10 gene (607063.0009) previously identified in a Bruck syndrome patient. In the other pedigree branch, both parents carried a deletion in the PPIB gene (123841.0004) causing lethal OI type IX (OI9; 259440) in their 2 children.


Nomenclature

The form of OI caused by mutation in the FKBP10 gene was originally designated OI type VI (OI6) in OMIM.


REFERENCES

  1. Alanay, Y., Avaygan, H., Camacho, N., Utine, G. E., Boduroglu, K., Aktas, D., Alikasifoglu, M., Tuncbilek, E., Orhan, D., Bakar, F. T., Zabel, B., Superti-Furga, A., and 12 others. Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am. J. Hum. Genet. 86: 551-559, 2010. Note: Erratum: Am. J. Hum. Genet. 87: 572-573, 2010. [PubMed: 20362275, images, related citations] [Full Text]

  2. Alanay, Y., Krakow, D. Response to Shaheen et al. (Letter) Am. J. Hum. Genet. 87: 308 only, 2010.

  3. 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]

  4. Kelley, B. P., Malfait, F., Bonafe, L., Baldridge, D., Homan, E., Symoens, S., Willaert, A., Elcioglu, N., Van Maldergem, L., Verellen-Dumoulin, C., Gillerot, Y., Napierala, D., Krakow, D., Beighton, P., Superti-Furga, A., De Paepe, A., Lee, B. Mutations in FKBP10 cause recessive osteogenesis imperfecta and Bruck syndrome. J. Bone Miner. Res. 26: 666-672, 2011. [PubMed: 20839288, images, related citations] [Full Text]

  5. Shaheen, R., Al-Owain, M., Sakati, N., Alzayed, Z. S., Alkuraya, F. S. FKBP10 and Bruck syndrome: phenotypic heterogeneity or call for reclassification? (Letter) Am. J. Hum. Genet. 87: 306-307, 2010. Note: Erratum: Am. J. Hum. Genet. 87: 571 only, 2010. [PubMed: 20696291, related citations] [Full Text]

  6. Steinlein, O. K., Aichinger, E., Trucks, H., Sander, T. Mutations in FKBP10 can cause a severe form of isolated osteogenesis imperfecta. BMC Med. Genet. 12: 152, 2011. Note: Electronic Article. [PubMed: 22107750, images, related citations] [Full Text]


Nara Sobreira - updated : 4/2/2013
Nara Sobreira - updated : 3/29/2013
Nara Sobreira - updated : 12/7/2012
Nara Sobreira - updated : 2/2/2012
Nara Sobreira - updated : 5/25/2011
Nara Sobreira - updated : 5/18/2011
Nara Sobreira - updated : 3/29/2011
Nara Sobreira - updated : 5/28/2010
Creation Date:
Kelly A. Przylepa : 4/24/2007
carol : 04/19/2017
alopez : 10/05/2016
carol : 04/03/2013
carol : 4/2/2013
carol : 4/2/2013
carol : 3/30/2013
carol : 3/29/2013
carol : 12/18/2012
terry : 12/17/2012
carol : 12/7/2012
carol : 2/2/2012
carol : 6/3/2011
terry : 5/25/2011
terry : 5/19/2011
carol : 5/18/2011
carol : 3/29/2011
carol : 3/29/2011
carol : 6/4/2010
carol : 6/3/2010
terry : 5/28/2010
carol : 9/11/2007
carol : 4/24/2007

# 610968

OSTEOGENESIS IMPERFECTA, TYPE XI; OI11


Alternative titles; symbols

OI, TYPE XI


ORPHA: 216812, 216820, 666;   DO: 0110351;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
17q21.2 Osteogenesis imperfecta, type XI 610968 Autosomal recessive 3 FKBP10 607063

TEXT

A number sign (#) is used with this entry because osteogenesis imperfecta type XI (OI11) is caused by homozygous or compound heterozygous mutation in the FKBP10 gene (607063) on chromosome 17q21.


Description

Osteogenesis imperfecta (OI) comprises a group of connective tissue disorders characterized by bone fragility and low bone mass. The disorder is clinically and genetically heterogeneous. OI type XI is an autosomal recessive form of OI (summary by Alanay et al., 2010).


Clinical Features

Alanay et al. (2010) studied 5 consanguineous families from northern Turkey in which a severe progressive deforming type of OI cosegregated with autosomal recessive epidermolysis bullosa simplex (131900), the latter resulting from a defect in keratin-14 (148066). Dentinogenesis imperfecta, a feature of OI type III (259420), was absent. The histologic features included a distorted lamellar structure and a fish scale-like pattern, along with elevated serum alkaline phosphatase. Alanay et al. (2010) also studied a Mexican family in which 3 sibs of consanguineous parents had severe progressive deforming OI.

Steinlein et al. (2011) described 3 German male sibs with a severe form of OI who were homozygous for a mutation in the FKBP10 gene (607063.0008). All 3 had dentinogenesis imperfecta and none showed contractures or webbing.


Inheritance

Alanay et al. (2010) confirmed autosomal recessive inheritance of OI type XI by the finding of homozygous mutations in the FKBP10 gene in affected members of 5 Turkish families and 1 Mexican family.


Mapping

In 5 consanguineous Turkish families segregating OI type XI and generalized epidermolysis bullosa simplex, the latter caused by mutation in the KRT14 gene, Alanay et al. (2010) determined that all affected individuals shared a 0.83-Mb region of homozygosity on chromosome 17q21.


Molecular Genetics

In affected members of 5 consanguineous Turkish families segregating autosomal recessive epidermolysis bullosa simplex (139100) and OI type XI, Alanay et al. (2010) identified homozygosity for 2 mutations: a missense mutation in the KRT14 gene (148066.0006) known to cause EB simplex and an in-frame deletion in the FKBP10 gene (607063.0001) causing OI. In 3 Mexican sibs with OI type XI, they identified homozygosity for a null mutation in the FKBP10 gene (607063.0002). Neither mutation was found in a panel of 210 alleles from ethnically matched unaffected individuals. The FKBP10 gene encodes a chaperone that participates in type I procollagen folding, and Alanay et al. (2010) determined that FKBP10 mutations affect type I procollagen secretion.

In 2 brothers with Bruck syndrome (BRKS1; 259450), Shaheen et al. (2010) identified a homozygous mutation in the FKBP10 gene (607063.0003). They suggested that their patients and the patients reported by Alanay et al. (2010) with OI may both have had Bruck syndrome and that bisphosphonate therapy may explain the less severe phenotype in their patients. In response to Shaheen et al. (2010), Alanay and Krakow (2010) noted that a wide phenotypic range of severity can result from different mutations in the same gene and suggested that the disorder caused by mutation in the FKBP10 gene be categorized as a recessive form of progressive deforming OI with or without joint contractures.

Kelley et al. (2011) sequenced the FKBP10 gene in 6 individuals from 5 families with a moderately severe OI phenotype, 4 with congenital joint contractures (Bruck syndrome; 259450) and 1 (patient 2) without contractures. The patient without contractures had a 35-bp deletion (607063.0004).

Barnes et al. (2012) identified a Palestinian pedigree with moderate and lethal forms of recessive OI caused by mutations in the FKBP10 or PPIB (123841) gene. In 1 pedigree branch, a child with moderate type XI OI was homozygous for the indel mutation in the FKBP10 gene (607063.0009) previously identified in a Bruck syndrome patient. In the other pedigree branch, both parents carried a deletion in the PPIB gene (123841.0004) causing lethal OI type IX (OI9; 259440) in their 2 children.


Nomenclature

The form of OI caused by mutation in the FKBP10 gene was originally designated OI type VI (OI6) in OMIM.


REFERENCES

  1. Alanay, Y., Avaygan, H., Camacho, N., Utine, G. E., Boduroglu, K., Aktas, D., Alikasifoglu, M., Tuncbilek, E., Orhan, D., Bakar, F. T., Zabel, B., Superti-Furga, A., and 12 others. Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am. J. Hum. Genet. 86: 551-559, 2010. Note: Erratum: Am. J. Hum. Genet. 87: 572-573, 2010. [PubMed: 20362275] [Full Text: https://doi.org/10.1016/j.ajhg.2010.02.022]

  2. Alanay, Y., Krakow, D. Response to Shaheen et al. (Letter) Am. J. Hum. Genet. 87: 308 only, 2010.

  3. 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]

  4. Kelley, B. P., Malfait, F., Bonafe, L., Baldridge, D., Homan, E., Symoens, S., Willaert, A., Elcioglu, N., Van Maldergem, L., Verellen-Dumoulin, C., Gillerot, Y., Napierala, D., Krakow, D., Beighton, P., Superti-Furga, A., De Paepe, A., Lee, B. Mutations in FKBP10 cause recessive osteogenesis imperfecta and Bruck syndrome. J. Bone Miner. Res. 26: 666-672, 2011. [PubMed: 20839288] [Full Text: https://doi.org/10.1002/jbmr.250]

  5. Shaheen, R., Al-Owain, M., Sakati, N., Alzayed, Z. S., Alkuraya, F. S. FKBP10 and Bruck syndrome: phenotypic heterogeneity or call for reclassification? (Letter) Am. J. Hum. Genet. 87: 306-307, 2010. Note: Erratum: Am. J. Hum. Genet. 87: 571 only, 2010. [PubMed: 20696291] [Full Text: https://doi.org/10.1016/j.ajhg.2010.05.020]

  6. Steinlein, O. K., Aichinger, E., Trucks, H., Sander, T. Mutations in FKBP10 can cause a severe form of isolated osteogenesis imperfecta. BMC Med. Genet. 12: 152, 2011. Note: Electronic Article. [PubMed: 22107750] [Full Text: https://doi.org/10.1186/1471-2350-12-152]


Contributors:
Nara Sobreira - updated : 4/2/2013
Nara Sobreira - updated : 3/29/2013
Nara Sobreira - updated : 12/7/2012
Nara Sobreira - updated : 2/2/2012
Nara Sobreira - updated : 5/25/2011
Nara Sobreira - updated : 5/18/2011
Nara Sobreira - updated : 3/29/2011
Nara Sobreira - updated : 5/28/2010

Creation Date:
Kelly A. Przylepa : 4/24/2007

Edit History:
carol : 04/19/2017
alopez : 10/05/2016
carol : 04/03/2013
carol : 4/2/2013
carol : 4/2/2013
carol : 3/30/2013
carol : 3/29/2013
carol : 12/18/2012
terry : 12/17/2012
carol : 12/7/2012
carol : 2/2/2012
carol : 6/3/2011
terry : 5/25/2011
terry : 5/19/2011
carol : 5/18/2011
carol : 3/29/2011
carol : 3/29/2011
carol : 6/4/2010
carol : 6/3/2010
terry : 5/28/2010
carol : 9/11/2007
carol : 4/24/2007