scholarly journals Mutations in FAM20C Are Associated with Lethal Osteosclerotic Bone Dysplasia (Raine Syndrome), Highlighting a Crucial Molecule in Bone Development

2007 ◽  
Vol 81 (5) ◽  
pp. 906-912 ◽  
Author(s):  
M.A. Simpson ◽  
R. Hsu ◽  
L.S. Keir ◽  
J. Hao ◽  
G. Sivapalan ◽  
...  
Keyword(s):  
Bone Development ◽  
Bone Dysplasia ◽  
Raine Syndrome

Raine syndrome: A rare lethal osteosclerotic bone dysplasia. Prenatal diagnosis, autopsy, and neuropathological findings

2007 ◽  
Vol 143A (24) ◽  
pp. 3280-3285 ◽  
Author(s):  
David Chitayat ◽  
Patrick Shannon ◽  
Sarah Keating ◽  
Ants Toi ◽  
Susan Blaser ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Bone Dysplasia ◽  
Raine Syndrome

scholarly journals Hypophosphataemic Rickets Secondary to Raine Syndrome: A Review of the Literature and Case Reports of Three Paediatric Patients’ Dental Management

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Lorna Hirst ◽  
Gehan Abou-Ameira ◽  
Simon Critchlow
Keyword(s):  
Autosomal Recessive ◽  
Case Reports ◽  
Autosomal Recessive Disorder ◽  
Bone Dysplasia ◽  
Hypophosphataemic Rickets ◽  
Tertiary Referral Hospital ◽  
Street Hospital ◽  
Great Ormond Street Hospital ◽  
Dental Management ◽  
Raine Syndrome

Raine Syndrome (RS) also referred to as lethal osteosclerotic bone dysplasia describes an exceptionally rare autosomal recessive disorder with an estimated prevalence of <1 in 1,000,000. Endocrinological manifestations such as hypophosphataemic rickets depict a recent finding within the phenotypic spectrum of nonlethal RS. The dental sequelae of hypophosphataemic rickets are significant. Spontaneous recurrent abscesses on noncarious teeth result in significant odontogenic pain and multiple dental interventions. The dental presentations of nonlethal RS are less widely described within the literature. Amelogenesis Imperfecta (AI), however, was recently postulated as a key characteristic. This article presents the dental manifestations and extensive restorative and oral surgical intervention of three siblings with hypophosphataemic rickets secondary to Raine Syndrome treated at Great Ormond Street Hospital for Children, a tertiary referral hospital.

scholarly journals Nonlethal Raine Syndrome in a Newborn Boy Caused by a Novel FAM20C Variant

2021 ◽  
pp. 1-5
Author(s):  
Nazan Eras ◽  
Yalcin Celik
Keyword(s):  
Genetic Disorder ◽  
Bone Dysplasia ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Limited Information ◽  
Sequencing Platform ◽  
Gene Sequence Analysis ◽  
Raine Syndrome

Raine syndrome (RS) is a rare genetic disorder characterized by osteosclerotic bone dysplasia caused by a homozygous mutation, compound heterozygous mutation, or microdeletion in the FAM20C gene. In the present study, the MiSeq next-generation sequencing platform was used to perform the FAM20C gene sequence analysis. A novel homozygous variant c.1255T>C (p.W419R) in the FAM20C gene was diagnosed, and a nonlethal RS phenotype was confirmed, thus contributing to the expansion of the nonlethal RS phenotype. Since there is limited information about rare diseases, we believe that these studies will contribute to the literature and to the understanding of how these disorders develop and progress.

An Activating Variant in CTNNB1 is Associated with a Sclerosing Bone Dysplasia and Adrenocortical Neoplasia

2020 ◽  
Vol 105 (3) ◽  
pp. 688-695 ◽  
Author(s):  
Hui Peng ◽  
Zandra A Jenkins ◽  
Ruby White ◽  
Sam Connors ◽  
Matthew F Hunter ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
Bone Development ◽  
Bone Dysplasia ◽  
Adrenocortical Adenoma ◽  
Gain Of Function ◽  
Sclerosing Bone Dysplasia ◽  
Whole Exome ◽  
De Novo Variant

Abstract Context The WNT/β-catenin pathway is central to the pathogenesis of various human diseases including those affecting bone development and tumor progression. Objective To evaluate the role of a gain-of-function variant in CTNNB1 in a child with a sclerosing bone dysplasia and an adrenocortical adenoma. Design Whole exome sequencing with corroborative biochemical analyses. Patients We recruited a child with a sclerosing bone dysplasia and an adrenocortical adenoma together with her unaffected parents. Intervention Whole exome sequencing and performance of immunoblotting and luciferase-based assays to assess the cellular consequences of a de novo variant in CTNNB1. Main Outcome Measure(s)/Result A de novo variant in CTNNB1 (c.131C&gt;T; p.[Pro44Leu]) was identified in a patient with a sclerosing bone dysplasia and an adrenocortical adenoma. A luciferase-based transcriptional assay of WNT signaling activity verified that the activity of β-catenin was increased in the cells transfected with a CTNNB1p.Pro44Leu construct (P = 4.00 × 10–5). The β-catenin p.Pro44Leu variant was also associated with a decrease in phosphorylation at Ser45 and Ser33/Ser37/Thr41 in comparison to a wild-type (WT) CTNNB1 construct (P = 2.16 × 10–3, P = 9.34 × 10–8 respectively). Conclusion Increased β-catenin activity associated with a de novo gain-of-function CTNNB1 variant is associated with osteosclerotic phenotype and adrenocortical neoplasia.

scholarly journals New Genes in Bone Development: What's New in Osteogenesis Imperfecta

2013 ◽  
Vol 98 (8) ◽  
pp. 3095-3103 ◽  
Author(s):  
Joan C. Marini ◽  
Angela R. Blissett
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Bone Development ◽  
Clinical Manifestations ◽  
Autosomal Recessive Inheritance ◽  
Bone Dysplasia ◽  
Protein Product ◽  
Type I ◽  
Related Condition ◽  
New Genes

Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by bone fragility and deformity and growth deficiency. Most cases of OI (classical types) have autosomal dominant inheritance and are caused by mutations in the type I collagen genes. During the past several years, a number of noncollagenous genes whose protein products interact with collagen have been identified as the cause(s) of rare forms of OI. This has led to a paradigm shift for OI as a collagen-related condition. The majority of the non-classical OI types have autosomal recessive inheritance and null mutations in their respective genes. The exception is a unique dominant defect in IFITM5, which encodes Bril and leads to hypertrophic callus and interosseous membrane ossification. Three recessive OI types arise from defects in any of the components of the collagen prolyl 3-hydroxylation complex (CRTAP, P3H1, CyPB), which modifies the collagen α1(I)Pro986 residue. Complex dysfunction leads to delayed folding of the procollagen triple helix and increased helical modification. Next, defects in collagen chaperones, HSP47 and FKBP65, lead to improper procollagen folding and deficient collagen cross-linking in matrix, respectively. A form of OI with a mineralization defect is caused by mutations in SERPINF1, whose protein product, PEDF, is a well-known antiangiogenesis factor. Defects in the C-propeptide cleavage enzyme, BMP1, also cause recessive OI. Additional genes, including SP7 and TMEM38B, have been implicated in recessive OI but are as yet unclassified. Elucidating the mechanistic pathways common to dominant and recessive OI may lead to novel therapeutic approaches to improve clinical manifestations.

Cranial crassicaudiasis in two coastal dolphin species from South Africa is predominantly a disease of immature individuals

2020 ◽  
Vol 139 ◽  
pp. 93-102 ◽  
Author(s):  
MF Van Bressem ◽  
P Duignan ◽  
JA Raga ◽  
K Van Waerebeek ◽  
N Fraijia-Fernández ◽  
...  
Keyword(s):  
South Africa ◽  
Bone Development ◽  
Bottlenose Dolphins ◽  
Fatal Outcome ◽  
Population Level ◽  
Cape Coast ◽  
Osteolytic Lesions ◽  
Immune Mediated ◽  
Significant Difference ◽  
The Difference

Crassicauda spp. (Nematoda) infest the cranial sinuses of several odontocetes, causing diagnostic trabecular osteolytic lesions. We examined skulls of 77 Indian Ocean humpback dolphins Sousa plumbea and 69 Indo-Pacific bottlenose dolphins Tursiops aduncus, caught in bather-protecting nets off KwaZulu-Natal (KZN) from 1970-2017, and skulls of 6 S. plumbea stranded along the southern Cape coast in South Africa from 1963-2002. Prevalence of cranial crassicaudiasis was evaluated according to sex and cranial maturity. Overall, prevalence in S. plumbea and T. aduncus taken off KZN was 13 and 31.9%, respectively. Parasitosis variably affected 1 or more cranial bones (frontal, pterygoid, maxillary and sphenoid). No significant difference was found by gender for either species, allowing sexes to be pooled. However, there was a significant difference in lesion prevalence by age, with immature T. aduncus 4.6 times more likely affected than adults, while for S. plumbea, the difference was 6.5-fold. As severe osteolytic lesions are unlikely to heal without trace, we propose that infection is more likely to have a fatal outcome for immature dolphins, possibly because of incomplete bone development, lower immune competence in clearing parasites or an over-exuberant inflammatory response in concert with parasitic enzymatic erosion. Cranial osteolysis was not observed in mature males (18 S. plumbea, 21 T. aduncus), suggesting potential cohort-linked immune-mediated resistance to infestation. Crassicauda spp. may play a role in the natural mortality of S. plumbea and T. aduncus, but the pathogenesis and population level impact remain unknown.

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