Assignment of gene responsible for progressive pseudorheumatoid dysplasia to chromosome 6 and examination of COL10A1 as candidate gene

El-Shanti, Hatem; Murray, Jeffrey C.; Semina, Elena V.; Beutow, Kenneth H; Scherpbier, Titia; Al-Alami, Jamil

doi:10.1038/sj.ejhg.5200187

Cited by 23 publications

(22 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…WISP3 (Wnt1 inducible signaling pathway protein 3) was found to be the causative gene for PPD in 1999 [Hurvitz et al, 1999], after a series of successful linkage studies on chromosome 6q22 in consanguineous families [El-Shanti et al, 1997a;Fischer et al, 1998]. The gene is composed of five coding exons, with several alternatively spliced exons described in the databases.…”

Section: Molecular Findingsmentioning

confidence: 99%

Molecular study of WISP3 in nine families originating from the Middle‐East and presenting with progressive pseudorheumatoid dysplasia: Identification of two novel mutations, and description of a founder effect

Delague

Chouery

Corbani

et al. 2005

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive syndrome characterized by the presence of spondyloepiphyseal dysplasia associated with pain, stiffness, and swelling of multiple joints, osteoporosis, and the absence of destructive bone changes. The disorder is caused by mutations of the WISP3 gene located on chromosome 6q22. We hereby report the molecular study of the WISP3 gene in nine unrelated consanguineous families originating from the Middle-East: three from Lebanon, five from Syria, and one from Palestinian Bedouin descent, all affected with PPD. Five different sequence variations were identified in the WISP3 gene, two of them being new mutations: the c.589G --> C transversion at codon 197, responsible for a splicing defect (A197fsX201); and the c.536_537delGT deletion (C179fsX), both in exon 3. In all other families, the affected patients were homozygous for a previously described nonsense mutation, namely c.156C --> A (C52X). Interestingly, in the latter families, the C52X mutation was always found associated with a novel c.248G --> A (G83E) variation, suggesting the existence of a founder effect.

show abstract

Section: Molecular Findingsmentioning

confidence: 99%

Molecular study of WISP3 in nine families originating from the Middle‐East and presenting with progressive pseudorheumatoid dysplasia: Identification of two novel mutations, and description of a founder effect

Delague

Chouery

Corbani

et al. 2005

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…29 Amplification of these markers was performed by PCR under standard conditions. 30 The amplified products were analysed on 6% denaturing polyacrylamide gel (8 M urea) and stained with silver nitrate according to standard protocols. 31 Statistical analysis LOD score analysis was performed using MLINK of the LINKAGE 5.1 computer program package.…”

Section: Subjectsmentioning

confidence: 99%

Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)

Ferguson

Chen

Tayeh

et al. 2005

Journal of Medical Genetics

363

269

View full text Add to dashboard Cite

Background: Majeed syndrome is an autosomal recessive, autoinflammatory disorder characterised by chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. The objectives of this study were to map, identify, and characterise the Majeed syndrome causal gene and to speculate on its function and role in skin and bone inflammation. Methods: Six individuals with Majeed syndrome from two unrelated families were identified for this study. Homozygosity mapping and parametric linkage analysis were employed for the localisation of the gene responsible for Majeed syndrome. Direct sequencing was utilised for the identification of mutations within the genes contained in the region of linkage. Expression studies and in silico characterisation of the identified causal gene and its protein were carried out. Results: The phenotype of Majeed syndrome includes inflammation of the bone and skin, recurrent fevers, and dyserythropoietic anaemia. The clinical picture of the six affected individuals is briefly reviewed. The gene was mapped to a 5.5 cM interval (1.8 Mb) on chromosome 18p. Examination of genes in this interval led to the identification of homozygous mutations in LPIN2 in affected individuals from the two families. LPIN2 was found to be expressed in almost all tissues. The function of LPIN2 and its role in inflammation remains unknown. Conclusions: We conclude that homozygous mutations in LPIN2 result in Majeed syndrome. Understanding the aberrant immune response in this condition will shed light on the aetiology of other inflammatory disorders of multifactorial aetiology including isolated chronic recurrent multifocal osteomyelitis, Sweet syndrome, and psoriasis.

show abstract

“…'other spondyloepi-(meta)-physeal [SE(M)D] dysplasias' (1). The incidence of PPD has been estimated at 1 individual per million in the UK (2), but it is likely to be higher in the Mediterranean, Middle East and Gulf states (3,4). No prevalent data on the Chinese population have been reported as yet.…”

Section: Introductionmentioning

confidence: 99%

Patients with progressive pseudorheumatoid dysplasia: From clinical diagnosis to molecular studies

Zhang

Qiu

et al. 2011

Mol Med Report

View full text Add to dashboard Cite

Abstract. Progressive pseudorheumatoid dysplasia (PPD) is a rare inherited autosomal recessive disease for which no prevalent data have been reported in China. We aimed to identify PPD based on clinical manifestations and imaging analysis of the bony skeleton and then to investigate gene mutations of Wnt1-inducible signaling pathway protein 3 (WISP3) in Chinese patients with PPD. Seven patients (aged 9-49 years) from six unrelated Chinese families all presented with a waddling gait, progressive swelling and restricted joint movements, and all were diagnosed as having PPD according to clinical signs and symptoms, as well as radiographic imaging. The radiographic imaging revealed no erosive arthropathy, but showed platyspondyly, irregular or wedged/ovoid anterior end-plates of the vertebral bodies, coxa vara and widened epiphyses or metaphyses including the femoral head and the metacarpophalangeal and interphalangeal joints. Normal laboratory values were found for the erythrocyte sedimentation rate, C-reactive protein and rheumatoid factors in all patients. Molecular studies revealed that five patients carried c.624_625insA/c.729_735delGAGAAAA, c.624_625insA/ c.866_867insA, c.866_867 insA/c.866_867insA, Q46X/ C114W and C223G/C114W mutations, respectively. In conclusion, our findings suggest that in order to avoid misdiagnosis, physicians should carefully examine the entire skeleton, including the spine, in addition to the skeletal extremities. Mutation analysis of the WISP3 gene is useful for confirming the clinical and radiographic diagnosis of PPD.

show abstract

Assignment of gene responsible for progressive pseudorheumatoid dysplasia to chromosome 6 and examination of COL10A1 as candidate gene

Cited by 23 publications

References 21 publications

Molecular study of WISP3 in nine families originating from the Middle‐East and presenting with progressive pseudorheumatoid dysplasia: Identification of two novel mutations, and description of a founder effect

Molecular study of WISP3 in nine families originating from the Middle‐East and presenting with progressive pseudorheumatoid dysplasia: Identification of two novel mutations, and description of a founder effect

Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)

Patients with progressive pseudorheumatoid dysplasia: From clinical diagnosis to molecular studies

Contact Info

Product

Resources

About