Entry - #616507 - OSTEOGENESIS IMPERFECTA, TYPE XVII; OI17 - OMIM
# 616507

OSTEOGENESIS IMPERFECTA, TYPE XVII; OI17


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
5q33.1 Osteogenesis imperfecta, type XVII 616507 AR 3 SPARC 182120
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
GROWTH
Height
- Short stature, variable
HEAD & NECK
Ears
- Normal hearing
Eyes
- White to slightly gray sclerae
Teeth
- Normal teeth
SKELETAL
- Osteoporosis
Spine
- Generalized platyspondyly
- Vertebral compression fractures
- Scoliosis
Limbs
- Joint hyperlaxity
- Long bone deformities (in some patients)
Hands
- Thin metacarpal cortices
SKIN, NAILS, & HAIR
Skin
- Soft skin
MUSCLE, SOFT TISSUES
- Muscle hypotonia
- Muscle weakness
- Decreased muscle mass
NEUROLOGIC
Central Nervous System
- Intraventricular hemorrhage (in some patients)
- Speech delay
- Motor delay
LABORATORY ABNORMALITIES
- Normal serum biochemistry
MISCELLANEOUS
- First fracture in early childhood
- Assisted ambulation or wheelchair-dependent
- Based on report of 2 unrelated girls (last curated August 2015)
MOLECULAR BASIS
- Caused by mutation in the cysteine-rich acidic secreted-protein gene (SPARC, 182120.0001)
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 III AD 3 259420 COL1A2 120160
7q21.3 Osteogenesis imperfecta, type IV AD 3 166220 COL1A2 120160
7q21.3 Osteogenesis imperfecta, type II AD 3 166210 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 XVII (OI17) is caused by homozygous mutation in the SPARC gene (182120) on chromosome 5q33.


Clinical Features

Mendoza-Londono et al. (2015) reported 2 unrelated girls with a clinical diagnosis of osteogenesis imperfecta type IV (OI4; 166220) in whom mutations in the SPARC gene were identified. One was a 14-year-old girl of North African origin who sustained her first fracture at 15 months of age, when she broke her right femur in a fall while trying to stand. X-rays at 19 months showed multiple vertebral compression fractures of the thoracic spine and kyphoscoliosis. By 4.4 years of age, she had sustained 10 long-bone fractures. Serum biochemistry was normal. Despite treatment with intravenous pamidronate, bone mineral density (BMD) remained low and scoliosis continued to increase, necessitating spinal fusion at 6.7 years of age. Other features included mild joint hyperlaxity, underdeveloped and weak muscles of the lower extremities, and bowing of both humeri, as well as expressive and comprehensive speech delay. At 14 years of age, the patient had short stature and had sustained approximately 1 long-bone fracture per year; she used a wheelchair for all mobility, having never achieved independent walking. Her parents had lumbar spine BMDs in the normal to low-normal range, and normal peripheral quantitative CT scans of the forearm. The second girl was born of consanguineous Indian parents and had left hip dislocation at age 10 weeks. She sustained her first low-trauma fracture at 5 years of age, a transverse femur fracture after a low-impact fall, and had 5 more fractures over the following 2 years. MRI of brain and spine at age 4 showed a large spinal canal with syrinx from T10 to T11, generalized platyspondyly, and thoracic kyphosis. Skeletal x-rays at age 6 showed compression fractures of most thoracic and lumbar vertebrae as well as mild kyphoscoliosis, and she had decreased lumbar spine BMD. Analysis of an iliac bone sample excluded a mineralization disorder, but was consistent with hypermineralization on the material level. Other features in this patient included motor delay, muscle hypotonia, lower extremity weakness, decreased calf muscle mass, joint hyperlaxity, and soft skin. No parent of the affected girls had a history of fractures.


Inheritance

The transmission pattern of OI17 in the families reported by Mendoza-Londono et al. (2015) was consistent with autosomal recessive inheritance.


Molecular Genetics

In 2 unrelated girls with OI17, Mendoza-Londono et al. (2015) performed whole-exome sequencing and identified homozygosity for missense variants in the SPARC gene, R166H (182120.0001) and E263K (182120.0002), respectively. No variants were detected in genes known to be associated with dominant or recessive OI. The mutations were present in heterozygosity in the unaffected parents and were not found in an in-house exome database or the dbSNP, 1000 Genomes Project, NHLBI/NHGRI Exome Project, or ExAC databases. Noting that SPARC is dynamically produced in blood vessels during central nervous system development, the authors suggested that an episode of intraventricular hemorrhage observed in the immediate postnatal period in the girl of North African origin could be related to the defect in SPARC.


REFERENCES

  1. Mendoza-Londono, R., Fahiminiya, S., Majewski, J., Care4Rare Canada Consortium, Tetreault, M., Nadaf, J., Kannu, P., Sochett, E., Howard, A., Stimec, J., Dupuis, L., Roschger, P., and 9 others. Recessive osteogenesis imperfecta caused by missense mutations in SPARC. Am. J. Hum. Genet. 96: 979-985, 2015. [PubMed: 26027498, images, related citations] [Full Text]


Creation Date:
Marla J. F. O'Neill : 8/5/2015
carol : 12/19/2022
alopez : 08/05/2015
mcolton : 8/5/2015

# 616507

OSTEOGENESIS IMPERFECTA, TYPE XVII; OI17


ORPHA: 216820, 666;   DO: 0110338;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
5q33.1 Osteogenesis imperfecta, type XVII 616507 Autosomal recessive 3 SPARC 182120

TEXT

A number sign (#) is used with this entry because of evidence that osteogenesis imperfecta type XVII (OI17) is caused by homozygous mutation in the SPARC gene (182120) on chromosome 5q33.


Clinical Features

Mendoza-Londono et al. (2015) reported 2 unrelated girls with a clinical diagnosis of osteogenesis imperfecta type IV (OI4; 166220) in whom mutations in the SPARC gene were identified. One was a 14-year-old girl of North African origin who sustained her first fracture at 15 months of age, when she broke her right femur in a fall while trying to stand. X-rays at 19 months showed multiple vertebral compression fractures of the thoracic spine and kyphoscoliosis. By 4.4 years of age, she had sustained 10 long-bone fractures. Serum biochemistry was normal. Despite treatment with intravenous pamidronate, bone mineral density (BMD) remained low and scoliosis continued to increase, necessitating spinal fusion at 6.7 years of age. Other features included mild joint hyperlaxity, underdeveloped and weak muscles of the lower extremities, and bowing of both humeri, as well as expressive and comprehensive speech delay. At 14 years of age, the patient had short stature and had sustained approximately 1 long-bone fracture per year; she used a wheelchair for all mobility, having never achieved independent walking. Her parents had lumbar spine BMDs in the normal to low-normal range, and normal peripheral quantitative CT scans of the forearm. The second girl was born of consanguineous Indian parents and had left hip dislocation at age 10 weeks. She sustained her first low-trauma fracture at 5 years of age, a transverse femur fracture after a low-impact fall, and had 5 more fractures over the following 2 years. MRI of brain and spine at age 4 showed a large spinal canal with syrinx from T10 to T11, generalized platyspondyly, and thoracic kyphosis. Skeletal x-rays at age 6 showed compression fractures of most thoracic and lumbar vertebrae as well as mild kyphoscoliosis, and she had decreased lumbar spine BMD. Analysis of an iliac bone sample excluded a mineralization disorder, but was consistent with hypermineralization on the material level. Other features in this patient included motor delay, muscle hypotonia, lower extremity weakness, decreased calf muscle mass, joint hyperlaxity, and soft skin. No parent of the affected girls had a history of fractures.


Inheritance

The transmission pattern of OI17 in the families reported by Mendoza-Londono et al. (2015) was consistent with autosomal recessive inheritance.


Molecular Genetics

In 2 unrelated girls with OI17, Mendoza-Londono et al. (2015) performed whole-exome sequencing and identified homozygosity for missense variants in the SPARC gene, R166H (182120.0001) and E263K (182120.0002), respectively. No variants were detected in genes known to be associated with dominant or recessive OI. The mutations were present in heterozygosity in the unaffected parents and were not found in an in-house exome database or the dbSNP, 1000 Genomes Project, NHLBI/NHGRI Exome Project, or ExAC databases. Noting that SPARC is dynamically produced in blood vessels during central nervous system development, the authors suggested that an episode of intraventricular hemorrhage observed in the immediate postnatal period in the girl of North African origin could be related to the defect in SPARC.


REFERENCES

  1. Mendoza-Londono, R., Fahiminiya, S., Majewski, J., Care4Rare Canada Consortium, Tetreault, M., Nadaf, J., Kannu, P., Sochett, E., Howard, A., Stimec, J., Dupuis, L., Roschger, P., and 9 others. Recessive osteogenesis imperfecta caused by missense mutations in SPARC. Am. J. Hum. Genet. 96: 979-985, 2015. [PubMed: 26027498] [Full Text: https://doi.org/10.1016/j.ajhg.2015.04.021]


Creation Date:
Marla J. F. O'Neill : 8/5/2015

Edit History:
carol : 12/19/2022
alopez : 08/05/2015
mcolton : 8/5/2015