Entry - #613849 - OSTEOGENESIS IMPERFECTA, TYPE XII; OI12 - OMIM
# 613849

OSTEOGENESIS IMPERFECTA, TYPE XII; OI12


Alternative titles; symbols

OI, TYPE XII


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
12q13.13 Osteogenesis imperfecta, type XII 613849 AR 3 SP7 606633
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
GROWTH
Height
- Short stature
HEAD & NECK
Head
- High, prominent forehead
Face
- Facial asymmetry, mild
- Prominent supraorbital ridges
- Midface hypoplasia
Ears
- Progressive hearing loss, severe-to-profound
Eyes
- Normal sclerae
- Prominent supraorbital ridges
Nose
- Depressed nasal bridge
Mouth
- Microstomia
- Micrognathia
- High-arched palate
Teeth
- Delayed teeth eruption
- No dentinogenesis imperfecta
CARDIOVASCULAR
Heart
- Congenital heart disease (rare)
CHEST
Ribs Sternum Clavicles & Scapulae
- Pectus carinatum
SKELETAL
- Repeated bone fractures
- Generalized osteoporosis
- Mild bone deformities
Skull
- Wormian bones
Spine
- Scoliosis, mild
Limbs
- Bowing of upper limbs
- Bowing of lower limbs
Hands
- Hyperextensibility of the interphalangeal joints
NEUROLOGIC
Central Nervous System
- Delayed motor milestones
MISCELLANEOUS
- Onset of fractures in the first or second decade of life
- Onset of hearing loss in the second decade of life
MOLECULAR BASIS
- Caused by mutation in the transcription factor Sp7 gene gene (SP7, 606633.0001)
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 of evidence that osteogenesis imperfecta type XII (OI12) is caused by homozygous mutation in the SP7 gene (606633) on chromosome 12q13.


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 XII is an autosomal recessive form characterized by recurrent fractures, mild bone deformations, generalized osteoporosis, delayed teeth eruption, progressive hearing loss, no dentinogenesis imperfecta, and white sclerae (summary by Lapunzina et al., 2010).


Clinical Features

Lapunzina et al. (2010) reported an 8-year-old Egyptian boy with osteogenesis imperfecta and normal sclerae, who was born to consanguineous parents related as second cousins. Clinical features included recurrent fractures beginning at 3 months of age, mild bone deformities, delayed tooth eruption, and normal hearing. The family had a history of a similarly affected sib who, in addition to OI, was diagnosed with a congenital heart condition and died at the age of 4 years.

Fiscaletti et al. (2018) studied 3 sibs with osteogenesis imperfecta who were born to consanguineous Iraqi parents. The proband was a 14-year-old boy who presented for evaluation of profound sensorineural hearing loss, but who also had a history of recurrent low-trauma fractures starting at age 13 years. Examination revealed short stature, white sclerae, mild facial asymmetry, high prominent forehead, prominent supraorbital ridges, midface hypoplasia, prominent ears, depressed nasal bridge, microstomia, and high-arched palate. He had a history of delayed tooth eruption but no evidence of dentinogenesis imperfecta. In addition, there was bilateral knee joint hyperlaxity with valgus deformity and mild scoliosis. Temporal bone CT scan revealed significant bilateral otospongiosis (osteosclerosis) and poor mineralization of the ossicles and petrous temporal bone. Spine x-rays showed thoracic platyspondyly and reduced vertebral body height at all levels, with pronounced vertebral crush fractures at the thoracolumbar junction. Skeletal survey showed generalized osteopenia and striking undertubulation of long bones, metatarsals, and metacarpals, with associated thickening of cortices; bone densitometry confirmed diffuse low bone mineral density. Transiliac bone biopsy revealed high cortical porosity, with long canals that traversed the cortex parallel to the periosteal surface. A younger brother, who presented at age 12 years with a femur fracture after minimal trauma, also exhibited short stature and similar craniofacial features and had moderately severe mixed hearing loss. A 9-year-old sister had a history of low-trauma fractures and low bone density, but did not have short stature or hearing loss.


Mapping

By homozygosity mapping in the Egyptian family segregating OI, Lapunzina et al. (2010) identified several regions of homozygosity, including a region on chromosome 12 containing the candidate gene SP7. They considered SP7 to be a good candidate because it encodes an osteoblast-specific transcription factor that had been shown in mice to be indispensable for bone formation (Nakashima et al., 2002).


Inheritance

The transmission pattern of OI12 in the patient reported by Lapunzina et al. (2010) was consistent with autosomal recessive inheritance.


Molecular Genetics

In an 8-year-old Egyptian boy with osteogenesis imperfecta and normal sclerae, Lapunzina et al. (2010) identified a homozygous single basepair deletion in the SP7/OSX gene (606633.0001). The parents were heterozygous for the mutation.

In a consanguineous Iraqi family in which 3 sibs had osteogenesis imperfecta, 2 of whom also had severe to profound hearing loss, Fiscaletti et al. (2018) performed massively parallel sequencing analysis of 13 known OI-associated genes and identified homozygosity for a missense mutation in the SP7 gene (R316C; 606633.0002). The proband was negative for mutation in 2 common deafness genes. Their consanguineous parents were heterozygous for the SP7 mutation, as were 3 unaffected sibs. The father met the criteria for adult osteoporosis, but had no craniofacial or skeletal anomalies or history of low-trauma fractures, and had normal hearing.


Nomenclature

The form of OI caused by mutation in the SP7 gene was originally designated OI type XI (OI11) in OMIM.


REFERENCES

  1. Fiscaletti, M., Biggin, A., Bennetts, B., Wong, K., Briody, J., Pacey, V., Birman, C., Munns, C. F. Novel variant in Sp7/Osx associated with recessive osteogenesis imperfecta with bone fragility and hearing impairment. Bone 110: 66-75, 2018. [PubMed: 29382611, related citations] [Full Text]

  2. Lapunzina, P., Aglan, M., Temtamy, S., Caparros-Martin, J. A., Valencia, M., Leton, R., Martinez-Glez, V., Elhossini, R., Amr, K., Vilaboa, N., Ruiz-Perez, V. L. Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta. Am. J. Hum. Genet. 87: 110-114, 2010. [PubMed: 20579626, images, related citations] [Full Text]

  3. Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J. M., Behringer, R. R., de Crombrugghe, B. The novel zinc finger-containing transcription factor Osterix is required for osteoblast differentiation and bone formation. Cell 108: 17-29, 2002. [PubMed: 11792318, related citations] [Full Text]


Marla J. F. O'Neill - updated : 08/31/2018
Nara Sobreira - updated : 2/2/2012
Creation Date:
Nara Sobreira : 3/29/2011
carol : 03/05/2024
joanna : 09/12/2018
carol : 09/04/2018
carol : 08/31/2018
carol : 02/12/2015
carol : 2/2/2012
carol : 4/5/2011
carol : 3/29/2011

# 613849

OSTEOGENESIS IMPERFECTA, TYPE XII; OI12


Alternative titles; symbols

OI, TYPE XII


ORPHA: 216820, 666;   DO: 0110348;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
12q13.13 Osteogenesis imperfecta, type XII 613849 Autosomal recessive 3 SP7 606633

TEXT

A number sign (#) is used with this entry because of evidence that osteogenesis imperfecta type XII (OI12) is caused by homozygous mutation in the SP7 gene (606633) on chromosome 12q13.


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 XII is an autosomal recessive form characterized by recurrent fractures, mild bone deformations, generalized osteoporosis, delayed teeth eruption, progressive hearing loss, no dentinogenesis imperfecta, and white sclerae (summary by Lapunzina et al., 2010).


Clinical Features

Lapunzina et al. (2010) reported an 8-year-old Egyptian boy with osteogenesis imperfecta and normal sclerae, who was born to consanguineous parents related as second cousins. Clinical features included recurrent fractures beginning at 3 months of age, mild bone deformities, delayed tooth eruption, and normal hearing. The family had a history of a similarly affected sib who, in addition to OI, was diagnosed with a congenital heart condition and died at the age of 4 years.

Fiscaletti et al. (2018) studied 3 sibs with osteogenesis imperfecta who were born to consanguineous Iraqi parents. The proband was a 14-year-old boy who presented for evaluation of profound sensorineural hearing loss, but who also had a history of recurrent low-trauma fractures starting at age 13 years. Examination revealed short stature, white sclerae, mild facial asymmetry, high prominent forehead, prominent supraorbital ridges, midface hypoplasia, prominent ears, depressed nasal bridge, microstomia, and high-arched palate. He had a history of delayed tooth eruption but no evidence of dentinogenesis imperfecta. In addition, there was bilateral knee joint hyperlaxity with valgus deformity and mild scoliosis. Temporal bone CT scan revealed significant bilateral otospongiosis (osteosclerosis) and poor mineralization of the ossicles and petrous temporal bone. Spine x-rays showed thoracic platyspondyly and reduced vertebral body height at all levels, with pronounced vertebral crush fractures at the thoracolumbar junction. Skeletal survey showed generalized osteopenia and striking undertubulation of long bones, metatarsals, and metacarpals, with associated thickening of cortices; bone densitometry confirmed diffuse low bone mineral density. Transiliac bone biopsy revealed high cortical porosity, with long canals that traversed the cortex parallel to the periosteal surface. A younger brother, who presented at age 12 years with a femur fracture after minimal trauma, also exhibited short stature and similar craniofacial features and had moderately severe mixed hearing loss. A 9-year-old sister had a history of low-trauma fractures and low bone density, but did not have short stature or hearing loss.


Mapping

By homozygosity mapping in the Egyptian family segregating OI, Lapunzina et al. (2010) identified several regions of homozygosity, including a region on chromosome 12 containing the candidate gene SP7. They considered SP7 to be a good candidate because it encodes an osteoblast-specific transcription factor that had been shown in mice to be indispensable for bone formation (Nakashima et al., 2002).


Inheritance

The transmission pattern of OI12 in the patient reported by Lapunzina et al. (2010) was consistent with autosomal recessive inheritance.


Molecular Genetics

In an 8-year-old Egyptian boy with osteogenesis imperfecta and normal sclerae, Lapunzina et al. (2010) identified a homozygous single basepair deletion in the SP7/OSX gene (606633.0001). The parents were heterozygous for the mutation.

In a consanguineous Iraqi family in which 3 sibs had osteogenesis imperfecta, 2 of whom also had severe to profound hearing loss, Fiscaletti et al. (2018) performed massively parallel sequencing analysis of 13 known OI-associated genes and identified homozygosity for a missense mutation in the SP7 gene (R316C; 606633.0002). The proband was negative for mutation in 2 common deafness genes. Their consanguineous parents were heterozygous for the SP7 mutation, as were 3 unaffected sibs. The father met the criteria for adult osteoporosis, but had no craniofacial or skeletal anomalies or history of low-trauma fractures, and had normal hearing.


Nomenclature

The form of OI caused by mutation in the SP7 gene was originally designated OI type XI (OI11) in OMIM.


REFERENCES

  1. Fiscaletti, M., Biggin, A., Bennetts, B., Wong, K., Briody, J., Pacey, V., Birman, C., Munns, C. F. Novel variant in Sp7/Osx associated with recessive osteogenesis imperfecta with bone fragility and hearing impairment. Bone 110: 66-75, 2018. [PubMed: 29382611] [Full Text: https://doi.org/10.1016/j.bone.2018.01.031]

  2. Lapunzina, P., Aglan, M., Temtamy, S., Caparros-Martin, J. A., Valencia, M., Leton, R., Martinez-Glez, V., Elhossini, R., Amr, K., Vilaboa, N., Ruiz-Perez, V. L. Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta. Am. J. Hum. Genet. 87: 110-114, 2010. [PubMed: 20579626] [Full Text: https://doi.org/10.1016/j.ajhg.2010.05.016]

  3. Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J. M., Behringer, R. R., de Crombrugghe, B. The novel zinc finger-containing transcription factor Osterix is required for osteoblast differentiation and bone formation. Cell 108: 17-29, 2002. [PubMed: 11792318] [Full Text: https://doi.org/10.1016/s0092-8674(01)00622-5]


Contributors:
Marla J. F. O'Neill - updated : 08/31/2018
Nara Sobreira - updated : 2/2/2012

Creation Date:
Nara Sobreira : 3/29/2011

Edit History:
carol : 03/05/2024
joanna : 09/12/2018
carol : 09/04/2018
carol : 08/31/2018
carol : 02/12/2015
carol : 2/2/2012
carol : 4/5/2011
carol : 3/29/2011