Hajdu–Cheney syndrome with severe dural ectasia

Avela, Kristiina; Valanne, Leena; Helenius, Ilkka; Mäkitie, Outi

doi:10.1002/ajmg.a.33510

Cited by 31 publications

(38 citation statements)

References 13 publications

(14 reference statements)

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“…''Coarse hair'' seen in the patient reported by Avela et al [2011] was shown and commented on in patient 2 included in Gripp et al [1997]. Similarly, the slender built with small muscle mass and little subcutaneous fat shown in Figure 2 in Avela et al [2011] strongly resembles that of patient 2 of Gripp et al [1997].…”

Section: To the Editormentioning

confidence: 78%

“…Table I compares the findings in the patient reported by Avela et al [2011] to those previously published in lateral meningocele syndrome.…”

Section: To the Editormentioning

confidence: 88%

“…The recent report by Avela et al [2011] describes a 6-year-old boy with severe dural ectasia, hypotonia, and unusual appearance suggestive of Hajdu-Cheney syndrome.…”

Section: To the Editormentioning

confidence: 99%

See 2 more Smart Citations

Lateral meningocele syndrome and Hajdu–Cheney syndrome: Different disorders with overlapping phenotypes

Gripp¹

2011

American J of Med Genetics Pt A

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Section: To the Editormentioning

confidence: 78%

“…Table I compares the findings in the patient reported by Avela et al [2011] to those previously published in lateral meningocele syndrome.…”

Section: To the Editormentioning

confidence: 88%

See 1 more Smart Citation

Lateral meningocele syndrome and Hajdu–Cheney syndrome: Different disorders with overlapping phenotypes

Gripp¹

2011

American J of Med Genetics Pt A

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Section: Notch2mentioning

confidence: 99%

“…Despite the pronounced skeletal abnormalities reported in Hajdu Cheney syndrome, little is known regarding the mechanisms underlying the bone loss or the effects of Notch2 gain-of-function in the skeleton. Information obtained from iliac crest bone biopsies has been inconclusive and reported in a small number of subjects with Hajdu Cheney syndrome (32)(33)(34)(35).The purpose of this work was to gain understanding on the Hajdu Cheney syndrome skeletal phenotype and the mechanisms involved. To this end, we created a mouse model reproducing the NOTCH2 mutation (6949C3 T) found in a subject affected by the disease and presenting with pronounced osteoporosis and fractures (28,30 …”

mentioning

confidence: 99%

Hajdu Cheney Mouse Mutants Exhibit Osteopenia, Increased Osteoclastogenesis, and Bone Resorption

Canalis¹,

Schilling²,

Yee

et al. 2016

Journal of Biological Chemistry

106

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Notch receptors are determinants of cell fate and function and play a central role in skeletal development and bone remodeling. Hajdu Cheney syndrome, a disease characterized by osteoporosis and fractures, is associated with NOTCH2 mutations resulting in a truncated stable protein and gain-of-function. We created a mouse model reproducing the Hajdu Cheney syndrome by introducing a 6955C3 T mutation in the Notch2 locus leading to a Q2319X change at the amino acid level. Notch2Q2319X heterozygous mutants were smaller and had shorter femurs than controls; and at 1 month of age they exhibited cancellous and cortical bone osteopenia. As the mice matured, cancellous bone volume was restored partially in male but not female mice, whereas cortical osteopenia persisted in both sexes. Cancellous bone histomorphometry revealed an increased number of osteoclasts and bone resorption, without a decrease in osteoblast number or bone formation. Osteoblast differentiation and function were not affected in Notch2 Q2319X cells. The pre-osteoclast cell pool, osteoclast differentiation, and bone resorption in response to receptor activator of nuclear factor B ligand in vitro were increased in Notch2 Q2319X mutants. These effects were suppressed by the ␥-secretase inhibitor LY450139. In conclusion, Notch2 Q2319X mice exhibit cancellous and cortical bone osteopenia, enhanced osteoclastogenesis, and increased bone resorption.Notch proteins are four single-pass transmembrane receptors that play a critical role in cell fate decisions ( Fig. 1) (1-4). Notch regulates cell renewal and plays a role in skeletal development and homeostasis and in osteoblast and osteoclast differentiation (4 -8). Jagged1 and -2 and DeltaLike1, -3, and -4 are the five classic Notch ligands (4). Notch-ligand interactions result in the proteolytic cleavage and release of the Notch intracellular domain (NICD), 2 which translocates to the nucleus to form a complex with recombination signal-binding protein for immunoglobulin J region (Rbpj) and Mastermind-like to regulate transcription (9 -12). This canonical signaling pathway leads to the transcription of Hairy Enhancer of Split (Hes)1, -5, and -7 and Hes related with YRPW motif (Hey)1, -2, and -L. Skeletal cells express Notch1, Notch2, and low levels of Notch3 transcripts (13-15). Activation of Notch in undifferentiated and differentiated osteoblasts inhibits cell differentiation and function and causes osteopenia (16,17). In contrast, activation of Notch1 in osteocytes causes a pronounced increase in bone mass due to a suppression of bone resorption (18). Results from the conditional inactivation of Notch1 and Notch2 in the developing skeleton confirmed the inhibitory role of Notch in osteoblastogenesis (6,19). Whereas substantial work has characterized the consequences of Notch1 gain-of-function in the skeleton, there is limited knowledge on the function of Notch2 in the postnatal skeleton. This knowledge is particularly important because Notch1 and Notch2 do not have redundant functions, and Notch1 inhibits, wh...

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Response to “Lateral Meningocele Syndrome and Hajdu–Cheney Syndrome: Different Disorders With Overlapping Phenotypes” by Gripp

Avela

Mäkitie

2011

American J of Med Genetics Pt A

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Hajdu–Cheney syndrome with severe dural ectasia

Cited by 31 publications

References 13 publications

Lateral meningocele syndrome and Hajdu–Cheney syndrome: Different disorders with overlapping phenotypes

Lateral meningocele syndrome and Hajdu–Cheney syndrome: Different disorders with overlapping phenotypes

Hajdu Cheney Mouse Mutants Exhibit Osteopenia, Increased Osteoclastogenesis, and Bone Resorption

Response to “Lateral Meningocele Syndrome and Hajdu–Cheney Syndrome: Different Disorders With Overlapping Phenotypes” by Gripp

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