Read by QxMD icon Read

Progressive osseous heteroplasia

Ali Birjandinejad, Mohammad-Hossein Taraz-Jamshidi, Sayyed Hadi Sayyed Hosseinian
Progressive osseous heteroplasia is a rare inherited disease that begins with skin ossification and proceeds into the deeper connective tissues. The disease should be distinguished from other genetic disorders of heterotopic ossification including fibrodysplasia ossificans progressiva (FOP) and Albright hereditary osteodystrophy (AHO). We report a case of progressive osseous heteroplasia in a twenty four years old male with a complaint of ankylosis of the entire upper left limb and digital cutaneous lesions and sparing of the other limbs and the axial skeleton...
June 2016: Archives of Bone and Joint Surgery
Francesca Marta Elli, Agnès Linglart, Intza Garin, Luisa de Sanctis, Paolo Bordogna, Virginie Grybek, Arrate Pereda, Federica Giachero, Elisa Verrua, Patrick Hanna, Giovanna Mantovani, Guiomar Perez de Nanclares
CONTEXT: The term pseudohypoparathyroidism (PHP) was coined to describe the clinical condition resulting from end-organ resistance to parathormone (rPTH), caused by genetic and/or epigenetic alterations within or upstream of GNAS. Though knowledge about PHP is growing, there are few data on the prevalence of underlying molecular defects. OBJECTIVE: The purpose of our study was to ascertain the relative prevalence of PHP-associated molecular defects. DESIGN: With a specially designed questionnaire, we collected data from all patients (n=407) clinically and molecularly characterized to date by expert referral centres in France, Italy and Spain...
July 18, 2016: Journal of Clinical Endocrinology and Metabolism
Susanne Thiele, Giovanna Mantovani, Anne Barlier, Valentina Boldrin, Paolo Bordogna, Luisa de Sanctis, Francesca Elli, Kathleen Freson, Intza Garin, Virginie Grybek, Patrick Hanna, Benedetta Izzi, Olaf Hiort, Beatriz Lecumberri, Arrate Pereda, Vrinda Saraff, Caroline Silve, Serap Turan, Alessia Usardi, Ralf Werner, Guiomar Perez de Nanclares, Agnès Linglart
OBJECTIVE: Disorders caused by impairments in the parathyroid hormone (PTH) signalling pathway are historically classified under the term pseudohypoparathyroidism (PHP), that encompasses rare, related but highly heterogeneous diseases with demonstrated (epi)genetic causes. The actual classification is based on the presence or absence of specific clinical and biochemical signs together with an in vivo response to exogenous PTH and the results of an in vitro assay to measure Gsa protein activity...
July 11, 2016: European Journal of Endocrinology
Rudolf Happle
Progressive osseous heteroplasia (POH) is a segmental disorder characterized by progressive heterotopic ossification that extends from dermal and subcutaneous tissues to deeper structures. So far, it has been taken as a rarely occurring bone disease with autosomal dominant inheritance. Here, arguments are presented in favor of the alternative concept that the disorder is merely a type 2 segmental manifestation of autosomal dominant GNAS inactivation disorders. Type 2 segmental mosaicism arises, in a heterozygous embryo, from a somatic mutational event that occurs at an early developmental stage, resulting in loss of the corresponding wild-type allele and giving rise to a homozygous or hemizygous cell clone...
May 2016: European Journal of Medical Genetics
Mustafa Kemal Demir, Zafer Orkun Toktaş, Akın Akakın, Baran Yılmaz, Tayfun Gürol, Yağmur Sarıtaş
No abstract text is available yet for this article.
December 1, 2015: Spine Journal: Official Journal of the North American Spine Society
Jing Yang, Philipp Andre, Ling Ye, Ying-Zi Yang
The Hedgehog (Hh) signalling pathway plays many important roles in development, homeostasis and tumorigenesis. The critical function of Hh signalling in bone formation has been identified in the past two decades. Here, we review the evolutionarily conserved Hh signalling mechanisms with an emphasis on the functions of the Hh signalling pathway in bone development, homeostasis and diseases. In the early stages of embryonic limb development, Sonic Hedgehog (Shh) acts as a major morphogen in patterning the limb buds...
June 2015: International Journal of Oral Science
Marie-Laure Kottler
Parental imprinting and the type of the genetic alteration play a determinant role in the phenotype expression of GNAS locus associated to pseudohypoparathyroidism (PHP). GNAS locus gives rise to several different messenger RNA transcripts that are derived from the paternal allele, the maternal allele, or both and can be either coding or non-coding. As a consequence, GNAS mutations lead to a wide spectrum of phenotypes. An alteration in the coding sequence of the gene leads to a haplo-insufficiency and a dysmorphic phenotype (Albright's syndrome or AHO)...
May 2015: Annales D'endocrinologie
Giovanna Mantovani, Francesca M Elli
The term pseudohypoparathryoidism (PHP) refers to a group of rare genetic and epigenetic disorders characterized by resistance to the action of parathyroid hormone (PTH) that activates cAMP signaling in target cells. Together with pseudohypoparathyroidism, Albright hereditary osteodystrophy (AHO) and progressive osseous heteroplasia (POH) represent rare, related and deeply impairing disorders encompassing heterogeneous features, such as brachydactyly, ectopic ossifications, short stature, mental retardation and endocrine deficiencies due to resistance to the action of different hormones...
May 2015: Annales D'endocrinologie
Maria H Lin, Nawaporn Numbenjapon, Emily L Germain-Lee, Pisit Pitukcheewanont
INTRODUCTION: Progressive osseous heteroplasia (POH) is a condition of invasive heterotopic ossification. Reports of patients with mild POH with Albright hereditary osteodystrophy (AHO), specifically pseudohypoparathyroidism type Ia (PHP Ia) with hormonal resistance, suggest the possibility of a common molecular basis. GNAS has been implicated to account for overlapping features of POH and PHP Ia. Case 1: A 4-year-old boy with obesity, speech delay, and expanding subcutaneous masses on buttock/forearm...
July 2015: Journal of Pediatric Endocrinology & Metabolism: JPEM
Robert J Pignolo, Girish Ramaswamy, John T Fong, Eileen M Shore, Frederick S Kaplan
Progressive osseous heteroplasia (POH) is an ultrarare genetic condition of progressive ectopic ossification. Most cases of POH are caused by heterozygous inactivating mutations of GNAS, the gene encoding the alpha subunit of the G-stimulatory protein of adenylyl cyclase. POH is part of a spectrum of related genetic disorders, including Albright hereditary osteodystrophy, pseudohypoparathyroidism, and primary osteoma cutis, that share common features of superficial ossification and association with inactivating mutations of GNAS...
2015: Application of Clinical Genetics
Manuel C Lemos, Rajesh V Thakker
Pseudohypoparathyroidism type 1a (PHP1a) is characterized by hypocalcaemia and hyperphosphatemia due to parathyroid hormone resistance, in association with the features of Albright's hereditary osteodystrophy (AHO). PHP1a is caused by maternally inherited inactivating mutations of Gs-alpha, which is encoded by a complex imprinted locus termed GNAS. Paternally inherited mutations can lead either to pseudopseudohypoparathyroidism (PPHP) characterized by AHO alone, or to progressive osseous heteroplasia (POH), characterized by severe heterotopic ossification...
January 2015: Human Mutation
Lixin Kan, John A Kessler
Heterotopic ossification (HO), acquired or hereditary, is featured by the formation of bone outside of the normal skeleton. Typical acquired HO is a common, debilitating condition associated with traumatic events. Cardiovascular calcification, an atypical form of acquired HO, is prevalent and associated with high rates of cardiovascular mortality. Hereditary HO syndromes, such as fibrodysplasia ossificans progressiva and progressive osseous heteroplasia, are rare, progressive, life-threatening disorders. The cellular origins of HO remain elusive...
May 2014: Orthopedics
Dirk E Schrander, Tim J Welting, Marjolein M J Caron, Jaap J P Schrander, Lodewijk W van Rhijn, Inge Körver-Keularts, Constance T R M Schrander-Stumpel
Progressive osseous heteroplasia (POH) (OMIM 166350) is a rare autosomal dominant condition, characterized by heterotopic ossification of the skin, subcutaneous fat, and deep connective tissue. This condition is distinct from Albright's hereditary osteodystrophy or McCune Albright syndrome (OMIM 103580) and fibrodysplasia ossificans progressiva (OMIM 135100). We present an unusual presentation of POH in a 7-year-old female child. The clinical features included a painful swelling on the left foot, with mechanical complaints...
September 2014: Journal of Pediatric Orthopedics. Part B
Dana M Cairns, Robert J Pignolo, Tomoya Uchimura, Tracy A Brennan, Carter M Lindborg, Meiqi Xu, Frederick S Kaplan, Eileen M Shore, Li Zeng
No abstract text is available yet for this article.
November 1, 2013: Journal of Clinical Investigation
Jean B Regard, Deepti Malhotra, Jelena Gvozdenovic-Jeremic, Michelle Josey, Min Chen, Lee S Weinstein, Jianming Lu, Eileen M Shore, Frederick S Kaplan, Yingzi Yang
Heterotopic ossification, the pathologic formation of extraskeletal bone, occurs as a common complication of trauma or in genetic disorders and can be disabling and lethal. However, the underlying molecular mechanisms are largely unknown. Here we demonstrate that Gαs restricts bone formation to the skeleton by inhibiting Hedgehog signaling in mesenchymal progenitor cells. In progressive osseous heteroplasia, a human disease caused by null mutations in GNAS, which encodes Gαs, Hedgehog signaling is upregulated in ectopic osteoblasts and progenitor cells...
November 2013: Nature Medicine
Nicolas Richard, Arnaud Molin, Nadia Coudray, Pauline Rault-Guillaume, Harald Jüppner, Marie-Laure Kottler
CONTEXT: Heterozygous GNAS inactivating mutations cause pseudohypoparathyroidism type Ia (PHP-Ia) when maternally inherited and pseudopseudohypoparathyroidism (PPHP)/progressive osseous heteroplasia (POH) when paternally inherited. Recent studies have suggested that mutations on the paternal, but not the maternal, GNAS allele could be associated with intrauterine growth retardation (IUGR) and thus small size for gestational age. OBJECTIVES: The aim of the study was to confirm and expand these findings in a large number of patients presenting with either PHP-Ia or PPHP/POH...
September 2013: Journal of Clinical Endocrinology and Metabolism
Dana M Cairns, Robert J Pignolo, Tomoya Uchimura, Tracy A Brennan, Carter M Lindborg, Meiqi Xu, Frederick S Kaplan, Eileen M Shore, Li Zeng
Progressive osseous heteroplasia (POH) is a rare developmental disorder of heterotopic ossification (HO) caused by heterozygous inactivating germline mutations in the paternal allele of the GNAS gene. Interestingly, POH lesions have a bewildering mosaic distribution. Using clinical, radiographic, and photographic documentation, we found that most of the 12 individuals studied had a lesional bias toward one side or the other, even showing exclusive sidedness. Most strikingly, all had a dermomyotomal distribution of HO lesions...
August 2013: Journal of Clinical Investigation
F M Elli, A M Barbieri, P Bordogna, P Ferrari, R Bufo, E Ferrante, E Giardino, P Beck-Peccoz, A Spada, G Mantovani
Progressive osseous heteroplasia (POH) is a rare autosomal dominant disorder of mesenchymal differentiation characterized by progressive heterotopic ossification (HO) of dermis, deep connective tissues and skeletal muscle. Usually, initial bone formation occurs during infancy as primary osteoma cutis (OC) then progressively extending into deep connective tissues and skeletal muscle over childhood. Most cases of POH are caused by paternally inherited inactivating mutations of GNAS gene. Maternally inherited mutations as well as epigenetic defects of the same gene lead to pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO)...
October 2013: Bone
S Zhang, F S Kaplan, E M Shore
Progressive osseous heteroplasia (POH) and fibrous dysplasia (FD) are genetic diseases of bone formation at opposite ends of the osteogenic spectrum: imperfect osteogenesis of the skeleton occurs in FD, while heterotopic ossification in skin, subcutaneous fat, and skeletal muscle forms in POH. POH is caused by heterozygous inactivating germline mutations in GNAS, which encodes G-protein subunits regulating the cAMP pathway, while FD is caused by GNAS somatic activating mutations. We used pluripotent mouse ES cells to examine the effects of Gnas dysregulation on osteoblast differentiation...
September 2012: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
M Bastepe
Gαs is a ubiquitous signaling protein necessary for the actions of many neurotransmitters, hormones, and autocrine/paracrine factors. Loss-of-function mutations within the gene encoding Gαs, GNAS, are responsible for multiple human diseases, including Albright's Hereditary Osteodystrophy, progressive osseous heteroplasia, and pseudohypoparathyroidism. Gain-of-function mutations in the same gene are found in various endocrine and nonendocrine tumors and in patients with McCune-Albright Syndrome and fibrous dysplasia of bone...
September 2012: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"