Entry - #615066 - OSTEOGENESIS IMPERFECTA, TYPE XIV; OI14 - OMIM
# 615066

OSTEOGENESIS IMPERFECTA, TYPE XIV; OI14


Alternative titles; symbols

OI, TYPE XIV


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
9q31.2 Osteogenesis imperfecta, type XIV 615066 AR 3 TMEM38B 611236
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
GROWTH
Height
- Short stature, mild-moderate (in some patients)
HEAD & NECK
Eyes
- Blue-grey sclerae, mild (in some patients)
Teeth
- Normal teeth
CHEST
Ribs Sternum Clavicles & Scapulae
- Thin ribs
SKELETAL
- Bone fragility
- Multiple fractures
- Osteopenia
Skull
- Thin calvarium cortex
- Wormian bones
Spine
- Scoliosis
Limbs
- Pseudoarthrosis
- Femoral bowing
- Tibial bowing
MISCELLANEOUS
- Onset of first fracture: prenatal-6 years
- Fracture frequency decreases after puberty
MOLECULAR BASIS
- Caused by mutation in transmembrane protein 38B (TMRM38B, 611236.0001)
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 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
17q21.33 Osteogenesis imperfecta, type II AD 3 166210 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 autosomal recessive osteogenesis imperfecta type XIV (OI14) can be caused by homozygous mutation in the TMEM38B gene (611236) on chromosome 9q31.


Description

Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most cases of OI are autosomal dominant with mutations in 1 of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160).

Shaheen et al. (2012) described osteogenesis imperfecta type XIV (OI14), an autosomal recessive form of the disorder characterized by variable degrees of severity of multiple fractures and osteopenia, with normal teeth, sclerae, and hearing. Fractures first occur prenatally or by age 6 years.


Clinical Features

Shaheen et al. (2012) described 3 consanguineous Saudi families with a history of fractures. The patients who were studied from these families ranged in age from 2.8 to 16 years. Occurrence of first fracture ranged from prenatal onset to 6 years of age. Most had variable degrees of severity of multiple fractures and osteopenia. None had blue sclerae, abnormal teeth, progressive hearing loss, or other organ involvement.


Mapping

By autozygosity and linkage mapping in 3 multiplex consanguineous Saudi families with OI, Shaheen et al. (2012) found linkage of the disorder to chromosome 9q31.1-q31.3.


Molecular Genetics

Shaheen et al. (2012) described 2 simplex and 11 multiplex families encompassing 27 patients with OI. By exome sequencing and haplotype analysis within a critical interval on chromosome 9 identified in 3 of the consanguineous Saudi families, Shaheen et al. (2012) identified a homozygous truncating deletion of exon 4 of the TMEM38B gene in affected members (611236.0001). In 6 other families, homozygous mutations were found in the previously described OI genes SERPINF1 (172860), CRTAP (605497), and LEPRE1 (610339). Gonadal or gonadal/somatic mosaic mutations in the COL1A1 or COL1A2 genes were identified in the remaining families.

Volodarsky et al. (2013) identified the same homozygous truncating deletion of exon 4 of the TMEM38B gene in affected members of 3 unrelated Israeli Bedouin consanguineous families segregating OI.


REFERENCES

  1. Shaheen, R., Alazami, A. M., Alshammari, M. J., Faqeih, E., Alhashmi, N., Mousa, N., Alsinani, A., Ansari, S., Alzahrani, F., Al-Owain, M., Alzayed, Z. S., Alkuraya, F. S. Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation. J. Med. Genet. 49: 630-635, 2012. [PubMed: 23054245, related citations] [Full Text]

  2. 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]

  3. Volodarsky, M., Markus, B., Cohen, I., Staretz-Chacham, O., Flusser, H., Landau, D., Shelef, I., Langer, Y., Birk, O. S. A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta. Hum. Mutat. 34: 582-586, 2013. [PubMed: 23316006, related citations] [Full Text]


Contributors:
Nara Sobreira - updated : 04/25/2013
Creation Date:
Nara Sobreira : 2/4/2013
carol : 04/25/2013
carol : 2/4/2013
carol : 2/4/2013

# 615066

OSTEOGENESIS IMPERFECTA, TYPE XIV; OI14


Alternative titles; symbols

OI, TYPE XIV


ORPHA: 216820, 666;   DO: 0110343;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
9q31.2 Osteogenesis imperfecta, type XIV 615066 Autosomal recessive 3 TMEM38B 611236

TEXT

A number sign (#) is used with this entry because autosomal recessive osteogenesis imperfecta type XIV (OI14) can be caused by homozygous mutation in the TMEM38B gene (611236) on chromosome 9q31.


Description

Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most cases of OI are autosomal dominant with mutations in 1 of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160).

Shaheen et al. (2012) described osteogenesis imperfecta type XIV (OI14), an autosomal recessive form of the disorder characterized by variable degrees of severity of multiple fractures and osteopenia, with normal teeth, sclerae, and hearing. Fractures first occur prenatally or by age 6 years.


Clinical Features

Shaheen et al. (2012) described 3 consanguineous Saudi families with a history of fractures. The patients who were studied from these families ranged in age from 2.8 to 16 years. Occurrence of first fracture ranged from prenatal onset to 6 years of age. Most had variable degrees of severity of multiple fractures and osteopenia. None had blue sclerae, abnormal teeth, progressive hearing loss, or other organ involvement.


Mapping

By autozygosity and linkage mapping in 3 multiplex consanguineous Saudi families with OI, Shaheen et al. (2012) found linkage of the disorder to chromosome 9q31.1-q31.3.


Molecular Genetics

Shaheen et al. (2012) described 2 simplex and 11 multiplex families encompassing 27 patients with OI. By exome sequencing and haplotype analysis within a critical interval on chromosome 9 identified in 3 of the consanguineous Saudi families, Shaheen et al. (2012) identified a homozygous truncating deletion of exon 4 of the TMEM38B gene in affected members (611236.0001). In 6 other families, homozygous mutations were found in the previously described OI genes SERPINF1 (172860), CRTAP (605497), and LEPRE1 (610339). Gonadal or gonadal/somatic mosaic mutations in the COL1A1 or COL1A2 genes were identified in the remaining families.

Volodarsky et al. (2013) identified the same homozygous truncating deletion of exon 4 of the TMEM38B gene in affected members of 3 unrelated Israeli Bedouin consanguineous families segregating OI.


REFERENCES

  1. Shaheen, R., Alazami, A. M., Alshammari, M. J., Faqeih, E., Alhashmi, N., Mousa, N., Alsinani, A., Ansari, S., Alzahrani, F., Al-Owain, M., Alzayed, Z. S., Alkuraya, F. S. Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation. J. Med. Genet. 49: 630-635, 2012. [PubMed: 23054245] [Full Text: https://doi.org/10.1136/jmedgenet-2012-101142]

  2. 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]

  3. Volodarsky, M., Markus, B., Cohen, I., Staretz-Chacham, O., Flusser, H., Landau, D., Shelef, I., Langer, Y., Birk, O. S. A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta. Hum. Mutat. 34: 582-586, 2013. [PubMed: 23316006] [Full Text: https://doi.org/10.1002/humu.22274]


Contributors:
Nara Sobreira - updated : 04/25/2013

Creation Date:
Nara Sobreira : 2/4/2013

Edit History:
carol : 04/25/2013
carol : 2/4/2013
carol : 2/4/2013