Clinical, radiological, and chondro-osseous findings in opsismodysplasia: survey of a series of 12 unreported cases

Cormier‐Daire, Valérie

doi:10.1136/jmg.40.3.195

Cited by 29 publications

(29 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…OPS is a rare, autosomal recessive chondrodysplasia first described in 1977 and is primarily characterized by delayed bone maturation (Zonana et al, 1977, Maroteaux et al, 1984, Cormier-Daire et al, 2003). Affected patients have rhizomelic micromelia, small hands and feet, relative macrocephaly and characteristic craniofacial abnormalities including a prominent brow ridge.…”

Section: Discussionmentioning

confidence: 99%

“…Radiographic findings reported include shortened long bones with markedly delayed epiphyseal ossification and severe platyspondyly. Histological analysis of fetal growth plate cartilage shows disorganized proliferative zones with near absent columnar organization (Cormier-Daire et al, 2003) suggesting that the poor mineralization and other bony defects are due to abnormal cartilage growth plate organization and chondrocyte differentiation. Disease severity is highly variable from neonatal death due to respiratory failure to survival through to adulthood.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia

Feist

Holden²,

Fitzgerald³

2016

Clinical Dysmorphology

View full text Add to dashboard Cite

Objective To identify the genetic basis of a severe skeletal lethal dysplasia. The main clinical features of two affected fetuses included: short limbs with flared metaphyses, bowed radii, femora and tibiae, irregular ossification of hands and feet and marked platyspondyly. Methods Affected and non-affected family members were subjected to whole exome sequencing followed by immunoblot analysis on amniocytes isolated from one of the affected individuals. Results Unique compound heterozygous variants in the INPPL1 (inositol polyphosphate phosphatase-like 1) gene encoding the SHIP2 protein were identified in both affected individuals. One variant was inherited from each unaffected parent. Both allelic variants, c.[ 2327-1G>C];[1150_1151delGA], are predicted to result in premature stop codons leading to nonsense-mediated mRNA decay of the mutant alleles and no production of SHIP2. The absence of SHIP2 was confirmed by immunoblot analysis of proband amniocytes. Conclusions This skeletal disorder is caused by the complete absence of SHIP2 protein. INPPL1 mutations have been reported in opsismodysplasia (OPS), an autosomal recessive skeletal dysplasias with significant delayed bone formation. Our finding highlights the critical role that INPPL1/SHIP2 plays in skeletal development.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia

Feist

Holden²,

Fitzgerald³

2016

Clinical Dysmorphology

View full text Add to dashboard Cite

show abstract

“…Autosomal recessive Rhizomelic Chondrodysplasia punctata type 1 can be excluded on clinical and radiological features. Other conditions that should be considered in the differential diagnosis of SMED SL-AC are opsismodysplasia, a severe neonatal dwarfism characterized by delayed bone maturation (Cormier-Daire et al, 2003), and metatropic dysplasia, which may feature cervical cord compression (due to odontoid hypoplasia) (Sohohat et al, 1989;Superti-Furga et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Sudden death in spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type

Dias

Cairns²,

Patel³

2009

Clinical Dysmorphology

View full text Add to dashboard Cite

The spondylo-meta-epiphyseal dysplasias are an expanding group of skeletal dysplasias with specific features differentiating each subtype. We review the precocious carpal mineralization, unique metacarpal shape, triangular distal phalanges and mushroom cloud-shaped proximal phalanges present at an early age in spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type (SMED SL-AC) and report two patients with clinical and radiographic features consistent with SMED SL-AC, who died suddenly because of spinal cord compression. The patients presented are female siblings, providing further evidence for autosomal recessive inheritance. Cervical cord compression is found in half of reported patients and is the major cause of mortality. SMED SL-AC should be added to the list of genetic causes of sudden death. Radiological features in the hand may be used in the first few years of life to support an early diagnosis and thus allow for prevention of premature demise.

show abstract

“…5,6,12 However, knockout mice studies provide little in the way of new insights. Inppl1 is expressed at embryonic day E14.5 in the developing limb.…”

Section: Mechanism Of Action In Skeletal Developmentmentioning

confidence: 99%

INPPL1 gene mutations in opsismodysplasia

Fradet

Fitzgerald

2016

J Hum Genet

View full text Add to dashboard Cite

The INPPL1 (inositol polyphosphate phosphatase-like 1) gene encodes the inositol phosphatase, SHIP2 (for src homology 2 domain-containing inositol phosphatase 2). SHIP2 functions to dephosphorylate, and negatively regulate, the lipid second messenger phosphatidylinositol (3,4,5)P3. SHIP2 has been well studied in the area of insulin resistance and obesity but has roles in cancer and other disorders. Recently, it was reported that mutations in INPPL1 cause opsismodysplasia, a rare, autosomal recessive severe skeletal dysplasia. This review focuses on the mutations associated with opsismodysplasia and explores the role of INPPL1/ SHIP2 in skeletal development.

show abstract

Clinical, radiological, and chondro-osseous findings in opsismodysplasia: survey of a series of 12 unreported cases

Cited by 29 publications

References 10 publications

Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia

Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia

Sudden death in spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type

INPPL1 gene mutations in opsismodysplasia

Contact Info

Product

Resources

About