Entry - #613848 - OSTEOGENESIS IMPERFECTA, TYPE X; OI10 - OMIM
# 613848

OSTEOGENESIS IMPERFECTA, TYPE X; OI10


Alternative titles; symbols

OI, TYPE X


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
11q13.5 Osteogenesis imperfecta, type X 613848 AR 3 SERPINH1 600943
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
GROWTH
Height
- Short stature
Weight
- Weight less than 5th centile
HEAD & NECK
Head
- Macrocephaly, relative
- Bitemporal narrowing
- Open anterior fontanel
- High forehead
- Prominent forehead
Face
- Triangular face
- Midface hypoplasia
Eyes
- Blue sclera (patient A)
- Shallow orbits (patient A)
Mouth
- Micrognathia
Teeth
- Dentinogenesis imperfecta (patient A)
RESPIRATORY
Lung
- Chronic lung disease (patient A)
CHEST
External Features
- Narrow chest
Ribs Sternum Clavicles & Scapulae
- Thin ribs
- Broad ribs
ABDOMEN
Gastrointestinal
- Pyloric stenosis (patient A)
GENITOURINARY
Internal Genitalia (Male)
- Inguinal hernia, bilateral (patient A)
Kidneys
- Renal stones, bilateral (patient A)
SKELETAL
- Bone fractures, multiple
- Osteopenia, generalized
- Bone deformities, multiple
Spine
- Platyspondyly
- Vertebral compression fractures
- Scoliosis
Limbs
- Short limbs, relative
- Bowing of long bones
- Genu valgum
- Joint laxity, generalized
NEUROLOGIC
Central Nervous System
- Hypotonia, generalized (patient A)
VOICE
- High-pitched voice (patient A)
MISCELLANEOUS
- Based on 2 sibs and an unrelated patient (patient A) (last curated October 2016)
MOLECULAR BASIS
- Caused by mutation in the serpin peptidase inhibitor, clade H, member 1 (SERPINH1, 600943.0002)
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 I AD 3 166200 COL1A1 120150
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
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 X (OI10) is caused by homozygous mutation in the SERPINH gene (600943) on chromosome 11q13.


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 X is an autosomal recessive form characterized by multiple bone deformities and fractures, generalized osteopenia, dentinogenesis imperfecta, and blue sclera (Christiansen et al., 2010).


Clinical Features

Christiansen et al. (2010) reported a child with a severe deforming form of OI who was born to a clinically normal consanguineous Saudi Arabian couple and was the only affected member in the extended family. At birth he was noted to have a triangular face, relative macrocephaly, bitemporal narrowing, blue sclerae, micrognathia, and relatively short limbs with bowing at the thighs. Radiographs of the chest showed thin ribs with healing fractures, a fracture of the right humerus, a healing fracture of the left humerus, and platyspondyly. A skeletal survey at the age of 1 month was consistent with the diagnosis of osteogenesis imperfecta. There were multiple bone deformities and fractures that involved the upper and lower extremities and ribs and generalized osteopenia. When he was 1 year old, bilateral renal stones were noticed with left pelviureteric junction obstruction that ultimately required left nephrectomy because of hydronephrosis and loss of renal function. He had chronic lung disease of unclear etiology and from the age of 1.5 years he required continuous oxygen by nasal cannula to maintain adequate oxygenation. He had small opalescent teeth consistent with dentinogenesis imperfecta. At age 3 years and 6 months he had sudden unexplained respiratory distress at home and died soon after arrival at the hospital. No autopsy was performed.

Duran et al. (2015) studied a consanguineous family in which a sister and brother (cases R92-020A and B, International Skeletal Dysplasia Registry) were diagnosed with a moderately severe form of OI at ages 4 years and 6 months, respectively. No fractures occurred during their first few months of life, but radiographs showed generalized osteopenia, large anterior fontanel and wormian bones in the skull, coxa valga, mild femoral bowing, reduced thorax size, and scoliosis with compression fractures in the vertebrae. Hyperextensibility was noted in the fingers, knees, and hips. Blue sclerae were not observed, nor was there dentinogenesis imperfecta or hearing loss.


Inheritance

The transmission pattern of OI10 in the patient reported by Christiansen et al. (2010) was consistent with autosomal recessive inheritance.


Molecular Genetics

Because the SERPINH1 gene encodes a collagen-binding protein that functions as a chaperone in the endoplasmic reticulum, Christiansen et al. (2010) screened for mutations in this gene in individuals with OI whose cells did not produce overmodified type I collagen. In a Saudi Arabian patient with severe deforming OI X, they identified a homozygous missense mutation (L78P; 600943.0002).

Using DNA from a 4-year-old girl with a moderately severe form of OI, Duran et al. (2015) analyzed the exon sequences of 9 known OI-associated genes and identified homozygosity for a missense mutation in the SERPINH1 gene (M237T; 600943.0003). Her unaffected third-cousin parents were heterozygous carriers of the mutation; DNA from her affected brother was not available. In experiments using cultured patient dermal fibroblasts, the authors demonstrated that protein levels of both HSP47 and FKBP65 (FKBP10, 607063; see OI11, 610968) were reduced and mislocalized, and proximity ligation assays indicated that the proteins interact in subcellular compartments. Duran et al. (2015) suggested that the similarity in phenotype between OI10 and OI11 might be explained by the similar consequences on type I procollagen synthesis.


REFERENCES

  1. Christiansen, H. E., Schwarze, U., Pyott, S. M., AlSwaid, A., Al Balwi, M., Alrasheed, S., Pepin, M. G., Weis, M. A., Eyre, D. R., Byers, P. H. Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta. Am. J. Hum. Genet. 86: 389-398, 2010. [PubMed: 20188343, images, related citations] [Full Text]

  2. Duran, I., Nevarez, L., Sarukhanov, A., Wu, S., Lee, K., Krejci, P., Weis, M., Eyre, D., Krakow, D., Cohn, D. H. HSP47 and FKBP65 cooperate in the synthesis of type I procollagen. Hum. Molec. Genet. 24: 1918-1928, 2015. [PubMed: 25510505, images, related citations] [Full Text]


Contributors:
Marla J. F. O'Neill - updated : 10/12/2016
Creation Date:
Nara Sobreira : 3/29/2011
carol : 03/05/2024
carol : 10/12/2016
carol : 08/20/2015
carol : 8/20/2015
alopez : 3/18/2015
mcolton : 3/17/2015
carol : 5/16/2011
carol : 3/29/2011

# 613848

OSTEOGENESIS IMPERFECTA, TYPE X; OI10


Alternative titles; symbols

OI, TYPE X


ORPHA: 216812, 666;   DO: 0110346;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
11q13.5 Osteogenesis imperfecta, type X 613848 Autosomal recessive 3 SERPINH1 600943

TEXT

A number sign (#) is used with this entry because of evidence that osteogenesis imperfecta X (OI10) is caused by homozygous mutation in the SERPINH gene (600943) on chromosome 11q13.


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 X is an autosomal recessive form characterized by multiple bone deformities and fractures, generalized osteopenia, dentinogenesis imperfecta, and blue sclera (Christiansen et al., 2010).


Clinical Features

Christiansen et al. (2010) reported a child with a severe deforming form of OI who was born to a clinically normal consanguineous Saudi Arabian couple and was the only affected member in the extended family. At birth he was noted to have a triangular face, relative macrocephaly, bitemporal narrowing, blue sclerae, micrognathia, and relatively short limbs with bowing at the thighs. Radiographs of the chest showed thin ribs with healing fractures, a fracture of the right humerus, a healing fracture of the left humerus, and platyspondyly. A skeletal survey at the age of 1 month was consistent with the diagnosis of osteogenesis imperfecta. There were multiple bone deformities and fractures that involved the upper and lower extremities and ribs and generalized osteopenia. When he was 1 year old, bilateral renal stones were noticed with left pelviureteric junction obstruction that ultimately required left nephrectomy because of hydronephrosis and loss of renal function. He had chronic lung disease of unclear etiology and from the age of 1.5 years he required continuous oxygen by nasal cannula to maintain adequate oxygenation. He had small opalescent teeth consistent with dentinogenesis imperfecta. At age 3 years and 6 months he had sudden unexplained respiratory distress at home and died soon after arrival at the hospital. No autopsy was performed.

Duran et al. (2015) studied a consanguineous family in which a sister and brother (cases R92-020A and B, International Skeletal Dysplasia Registry) were diagnosed with a moderately severe form of OI at ages 4 years and 6 months, respectively. No fractures occurred during their first few months of life, but radiographs showed generalized osteopenia, large anterior fontanel and wormian bones in the skull, coxa valga, mild femoral bowing, reduced thorax size, and scoliosis with compression fractures in the vertebrae. Hyperextensibility was noted in the fingers, knees, and hips. Blue sclerae were not observed, nor was there dentinogenesis imperfecta or hearing loss.


Inheritance

The transmission pattern of OI10 in the patient reported by Christiansen et al. (2010) was consistent with autosomal recessive inheritance.


Molecular Genetics

Because the SERPINH1 gene encodes a collagen-binding protein that functions as a chaperone in the endoplasmic reticulum, Christiansen et al. (2010) screened for mutations in this gene in individuals with OI whose cells did not produce overmodified type I collagen. In a Saudi Arabian patient with severe deforming OI X, they identified a homozygous missense mutation (L78P; 600943.0002).

Using DNA from a 4-year-old girl with a moderately severe form of OI, Duran et al. (2015) analyzed the exon sequences of 9 known OI-associated genes and identified homozygosity for a missense mutation in the SERPINH1 gene (M237T; 600943.0003). Her unaffected third-cousin parents were heterozygous carriers of the mutation; DNA from her affected brother was not available. In experiments using cultured patient dermal fibroblasts, the authors demonstrated that protein levels of both HSP47 and FKBP65 (FKBP10, 607063; see OI11, 610968) were reduced and mislocalized, and proximity ligation assays indicated that the proteins interact in subcellular compartments. Duran et al. (2015) suggested that the similarity in phenotype between OI10 and OI11 might be explained by the similar consequences on type I procollagen synthesis.


REFERENCES

  1. Christiansen, H. E., Schwarze, U., Pyott, S. M., AlSwaid, A., Al Balwi, M., Alrasheed, S., Pepin, M. G., Weis, M. A., Eyre, D. R., Byers, P. H. Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta. Am. J. Hum. Genet. 86: 389-398, 2010. [PubMed: 20188343] [Full Text: https://doi.org/10.1016/j.ajhg.2010.01.034]

  2. Duran, I., Nevarez, L., Sarukhanov, A., Wu, S., Lee, K., Krejci, P., Weis, M., Eyre, D., Krakow, D., Cohn, D. H. HSP47 and FKBP65 cooperate in the synthesis of type I procollagen. Hum. Molec. Genet. 24: 1918-1928, 2015. [PubMed: 25510505] [Full Text: https://doi.org/10.1093/hmg/ddu608]


Contributors:
Marla J. F. O'Neill - updated : 10/12/2016

Creation Date:
Nara Sobreira : 3/29/2011

Edit History:
carol : 03/05/2024
carol : 10/12/2016
carol : 08/20/2015
carol : 8/20/2015
alopez : 3/18/2015
mcolton : 3/17/2015
carol : 5/16/2011
carol : 3/29/2011