Posts Categorized: Part 22: CONNECTIVE TISSUE

ACVR1 R206H receptor mutation: a “gain of function” mutation cause of fibrodysplasia ossificans progressiva

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Hatsell et al (Sci Transl Med. 2015 Sep 2;7(303):303ra137. doi: 10.1126/scitranslmed.aac4358) recently published very exciting work on the mechanism of the common ACVR1 gene mutation underlying fibrodysplasia ossificans progressive (FOP). This mutation confers the ability of the BMP 1 receptor ACVR1 to respond to  the inflammatory response ligand Activin A, and induce bone formation. This mechanism explains […]

Statin treatment for FGFR3 skeletal dysplasia phenotypes.

Posted by & filed under Part 22: CONNECTIVE TISSUE.

A paper published in Nature in September 2014 suggests that statins could represent a medical treatment for infants and children with thanatophoric dysplasia type I (TD1) and achondroplasia (ACH) due to gain-of-function mutations in the fibroblast growth factor receptor 3 gene (FGFR3). The authors showed that statin treatment can rescue patient-specific induced pluripotent stem cell (iPSC) […]

Abnormal signaling triggers cardiomyopathy in mice with Marfan syndrome

Posted by & filed under Part 22: CONNECTIVE TISSUE.

Francesco Ramirez’s group found that abnormal extracellular matrix (ECM) signaling results in dilated cardiomyopathy (DCM) in fibrillin 1–deficient mice. These mice develop enlarged and dysfunctional heart, altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including increased angiotensin II type I receptor (AT1R) signaling. Consistent with abnormal mechanosignaling, normal cardiac size and function […]

RNA interference-based therapy for transthyretin amyloidosis

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Transthyretin amyloidosis is caused by deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and heart. A paper recently published in the New England Journal of Medicine reports the safety and efficacy of a potent antitransthyretin small interfering RNA (RNAi) encapsulated in lipid nanoparticles and injected in patients with transthyretin amyloidosis. The RNAi resulted in sustained reduction of […]

Yunis-Varón syndrome gene identification links this skeletal dysplasia with neurological involvement to phosphoinositide metabolism


Yunis-Varón syndrome is a skeletal dyplasia with features of cleidocranial dysplasia, with digital hypoplasia and severe neurological involvement ( Through exome sequencing, we identified three families with mutations of FIG4, encoding a phosphoinositide phosphatase. This enzyme had previously been implicated in Charcot-Marie-Tooth type 4J (CMT-4J). While CMT-4J is usually caused by a combination of a […]

WNT1 mutations are responsible for early-onset osteoporosis and osteogenesis imperfecta

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Three independent studies have shown that WNT1 mutations are responsible for bone fragility. WNT1 mutations were found in families with moderately severe recessive osteogenesis imperfecta and early-onset osteoporosis. WNT1 is a secreted signaling protein that binds the frizzled receptor (FZD) and the co-receptor low-density lipoprotein-receptor-related protein 5 (LRP5). Biallelic loss-of-function mutations in LRP5 result in recessive […]

Mutations in the nucleoside transporter gene SLC29A3 cause dysosteosclerosis, a form of osteopetrosis.

Posted by & filed under New IEM, Part 16: LYSOSOMAL DISORDERS, Part 22: CONNECTIVE TISSUE.

SLC29A3 is a lysosomal nucleoside transporter mutations in which cause histiocytosis–lymphadenopathy plus syndrome, a group of conditions with little or no skeletal involvement. We have now identified mutations in this gene in dysosteosclerosis, a form of osteopetrosis characterized by the additional features of platyspondyly, remarkable acquired metaphyseal osteosclerosis and red-violet macular atrophy of skin. We […]

Mutations in histone acetyltransferase KAT6B cause Genitopatellar syndrome.

Posted by & filed under Exome sequencing, Part 22: CONNECTIVE TISSUE, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

Sorry to blow my own horn but I’m quite passionate about the findings described below. Late last year, the group of Clayton-Smith et al. identified mutations in KAT6B in Ohdo syndrome, a condition characterized by blepharophimosis and developmental delay. Shortly after, our group and the group of Simpson et al. identified mutations in the same […]

Enzyme replacement therapy in ectodermal dysplasia

Posted by & filed under Part 22: CONNECTIVE TISSUE, Treatment.

Significant Correction of Disease after Postnatal Administration of Recombinant Ectodysplasin A in Canine X-Linked Ectodermal Dysplasia Margret L. Casal, John R. Lewis, Elizabeth A. Mauldin, Aubry Tardivel, Karine Ingold, Manuel Favre, Fabrice Paradies,* Ste´phane Demotz, Olivier Gaide, and Pascal Schneider The American Journal of Human Genetics, volume 81 (2007) This paper describes the application of […]

Phenotypic variability of Shwachman–Bodian–Diamond syndrome gene mutations

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  Mutations in the Shwachman–Bodian–Diamond syndrome gene mutations can also give rise to a neonatal for of spondylometaphysial dysplasia. The Shwachman–Bodian–Diamond syndrome gene mutations cause a neonatal form of spondylometaphysial dysplasia (SMD) resembling SMD Sedaghatian type Gen Nishimura, Eiji Nakashima, Yuichiro Hirose, Trevor Cole, Phillip Cox, Daniel H Cohn, David L Rimoin, Ralph S Lachman, […]