Cartilage hair hypoplasia: Characteristics and orthopaedic manifestations

Riley, Patrick; Weiner, Dennis S.; Leighley, Bonnie; Jonah, David; Morton, D. Holmes; Strauss, Kevin A.; Bober, Michael B.; Dicintio, Martin S.

doi:10.1007/s11832-015-0646-z

Cited by 13 publications

(21 citation statements)

References 61 publications

(73 reference statements)

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“…Furthermore, in ceratohyal bone, the chondrocytes were distributed as multilayer cells and arranged in disorder in rmrp mutants, whereas WT chondrocytes in this bone stack like coins and are arranged in a one‐cell‐wide row. These results are consistent with the observed deficiency in columnar organization and widened metaphases of CHH patients …”

Section: Discussionsupporting

confidence: 92%

“…Dwarfism and short, thickened long bones with scalloped and widened metaphases are hallmarks of CHH patients . We sought to reveal the mechanisms of chondrodysplasia in CHH patients by examining the chondrogenesis in rmrp KO zebrafish.…”

Section: Discussionmentioning

confidence: 99%

“…The most prevalent hallmark of CHH is the disproportionate short‐limb short stature with short and thickened long bones, which is usually recognized in the newborn and occasionally in the prenatal stage . The abnormalities of tubular bone include widened, scalloped, and irregularly sclerotic metaphyses . Typically, the ossification centers of the epiphyses are radiographically normal in CHH patients with a mostly normal bone density …”

Section: Introductionmentioning

confidence: 99%

“…The abnormalities of tubular bone include widened, scalloped, and irregularly sclerotic metaphyses . Typically, the ossification centers of the epiphyses are radiographically normal in CHH patients with a mostly normal bone density …”

Section: Introductionmentioning

confidence: 99%

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Rmrp Mutation Disrupts Chondrogenesis and Bone Ossification in Zebrafish Model of Cartilage-Hair Hypoplasia via Enhanced Wnt/β-Catenin Signaling

Sun

Zhang

Liu

et al. 2019

Journal of Bone and Mineral Research

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Cartilage‐hair hypoplasia (CHH) is an autosomal recessive metaphyseal chondrodysplasia characterized by bone dysplasia and many other highly variable features. The gene responsible for CHH is the RNA component of the mitochondrial RNA‐processing endoribonuclease (RMRP) gene. Currently, the pathogenesis of osteochondrodysplasia and extraskeletal manifestations in CHH patients remains incompletely understood; in addition, there are no viable animal models for CHH. We generated an rmrp KO zebrafish model to study the developmental mechanisms of CHH. We found that rmrp is required for the patterning and shaping of pharyngeal arches. Rmrp mutation inhibits the intramembranous ossification of skull bones and promotes vertebrae ossification. The abnormalities of endochondral bone ossification are variable, depending on the degree of dysregulated chondrogenesis. Moreover, rmrp mutation inhibits cell proliferation and promotes apoptosis through dysregulating the expressions of cell‐cycle‐ and apoptosis‐related genes. We also demonstrate that rmrp mutation upregulates canonical Wnt/β‐catenin signaling; the pharmacological inhibition of Wnt/β‐catenin could partially alleviate the chondrodysplasia and increased vertebrae mineralization in rmrp mutants. Our study, by establishing a novel zebrafish model for CHH, partially reveals the underlying mechanism of CHH, hence deepening our understanding of the role of rmrp in skeleton development.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rmrp Mutation Disrupts Chondrogenesis and Bone Ossification in Zebrafish Model of Cartilage-Hair Hypoplasia via Enhanced Wnt/β-Catenin Signaling

Sun

Zhang

Liu

et al. 2019

Journal of Bone and Mineral Research

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“…Cartilage hair hypoplasia is found primarily in the Amish in Pennsylvania and the Finnish population . A mutation in RMRP (endoribonuclease RNase MRP) participates in cleavage of mitochondrial primers responsible for DNA replication and on pre‐rRNA processing in the nucleolus.…”

Section: Selected Primary Immunodeficiencies With Skin Signsmentioning

confidence: 99%

Skin signs of primary immunodeficiencies: how to find the genes to check

et al. 2018

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Primary immunodeficiencies (PIDs) are a heterogeneous group of rare diseases that result from defects in immune system development and/or function. The clinical manifestations of PIDs are highly variable, but most disorders involve at least an increased susceptibility to infection. Furthermore, cutaneous manifestations are very common in PIDs. As an easily accessible organ, the skin can be crucial for early diagnosis and treatment. This is relevant for preventing significant disease-associated morbidity and mortality. We provide a table that enables the reader to find the possible diseases and corresponding gene defects based on the skin manifestations of the suspected PIDs. To our knowledge, this is the first review that allows the reader to find relevant PIDs and the respective gene defects through solitary or combined skin signs.

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Clinical and molecular diagnosis of a cartilage‐hair hypoplasia with IGF‐1 deficiency

Castilla‐Cortázar

Ita

Martín-Estal

et al. 2016

American J of Med Genetics Pt A

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Cartilage-hair hypoplasia syndrome (CHH) is a rare autosomal recessive condition characterized by metaphyseal chondrodysplasia and characteristic hair, together with a myriad of other symptoms, being most common immunodeficiency and gastrointestinal complications. A 15-year-old Mexican male initially diagnosed with Hirschsprung disease and posterior immunodeficiency, presents to our department for genetic and complementary evaluation for suspected CHH. Physical, biochemical, and genetic studies confirmed CHH together with IGF-1 deficiency. For this reason, we propose IGF-1 replacement therapy for its well-known actions on hematopoiesis, immune function and maturation, and metabolism. Ó 2016 Wiley Periodicals, Inc.Key words: cartilage-hair hypoplasia; IGF-1; RMRP gene; GHR INTRODUCTIONCartilage-hair hypoplasia syndrome (CHH) is a rare autosomal recessive condition that was originally described by McKusik in 1964 in Amish children. In this population, it accounts for one in 1,300 newborns [McKusick et al., 1965], while in the Finnish population it accounts for one in 23,000 newborns [M€ akitie and Kaitila, 1993]. Outside those populations it is extremely rare, with no incidence data available [M€ akitie and Kaitila, 1993]. The genetic locus for this disease falls within the RNA Component Of Mitochondrial RNA Processing Endoribonuclease (RMRP) gene, localized in chromosome 9p12, which codes for the RMRP, believed to be required for cell cycle, mtDNA replication and rRNA processing [Ridanp€ a€ a et al., 2001;Hermanns et al., 2005;Thiel et al., 2005;Martin and Li, 2007]. The RMRP RNA product associates with at least seven proteins whose interactions and roles remain to be discovered [Welting et al., 2004].The hallmark of this condition is a metaphyseal chondrodysplasia and characteristic hair (fine, sparse with scalp, blond eyelashes-93%), with other several signs and symptoms including short stature and skeletal dysplasia (100%) with varum deformation of lower extremities, hypoplastic anemia during childhood (79%), immunodeficiency (during childhood they may present different recurrent infections secondary to an immunodeficiency that may be humoral, B-cell or T-cell, or combined-56%) [Pierce and Polmar, 1982;M€ akitie et al., 1998, 2000bBaradaran-Heravi et al., 2008] with higher risk of malignancies, skin and nails abnormalities, gastrointestinal diseases (such as Hirschsprung disease [HD], malabsorption, anal stenosis and esophageal atresia-18%) [M€ akitie et al., 2002, 2000a], and failure to thrive [M€ akitie et al., 1992;Glass and Tifft, 1999;Riley et al., 2015]. The growth failure is progressive, owing, partly, to a weak or absent pubertal growth spurt; pubertal maturation is normal; testicular size is abnormal in some patients with normal serum concentrations of testosterone, inhibin B and gonadotropins [M€ akitie et al., 2001].These patients are symptomatic since birth, showing short-limb dwarfism and short puffy hands, with normal head circumference [Giedion, 1998]. The final adult heights range from 100.7 t...

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Cartilage hair hypoplasia: Characteristics and orthopaedic manifestations

Cited by 13 publications

References 61 publications

Rmrp Mutation Disrupts Chondrogenesis and Bone Ossification in Zebrafish Model of Cartilage-Hair Hypoplasia via Enhanced Wnt/β-Catenin Signaling

Rmrp Mutation Disrupts Chondrogenesis and Bone Ossification in Zebrafish Model of Cartilage-Hair Hypoplasia via Enhanced Wnt/β-Catenin Signaling

Skin signs of primary immunodeficiencies: how to find the genes to check

Clinical and molecular diagnosis of a cartilage‐hair hypoplasia with IGF‐1 deficiency

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