A Patient With Rothmund-Thomson Syndrome and All Features of RAPADILINO

Kellermayer, Richárd; Siitonen, H. Annika; Hadzsiev, Kinga; Kestilä, Marjo; Kosztolányi, György

doi:10.1001/archderm.141.5.617

Cited by 22 publications

(15 citation statements)

References 23 publications

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“…In contrast to RTS, RAPADILINO syndrome is more common in females than in males. Furthermore, only one out of the 15 RAPADILINO patients diagnosed so far has developed malignant tumours, mainly osteosarcomas (Kellermayer et al, 2005). However, to date, no study has documented the risk of osteosarcoma over time.…”

Section: Introductionmentioning

confidence: 99%

p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization

Dietschy

Shevelev

Peña-Dı́az

et al. 2009

Journal of Cell Science

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RECQL4 belongs to the conserved RecQ family of DNA helicases, members of which play important roles in the maintenance of genome stability in all organisms that have been examined. Although genetic alterations in the RECQL4 gene are reported to be associated with three autosomal recessive disorders (Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes), the molecular role of RECQL4 still remains poorly understood. Here, we show that RECQL4 specifically interacts with the histone acetyltransferase p300 (also known as p300 HAT), both in vivo and in vitro, and that p300 acetylates one or more of the lysine residues at positions 376, 380, 382, 385 and 386 of RECQL4. Furthermore, we report that these five lysine residues lie within a short motif of 30 amino acids that is essential for the nuclear localization of RECQL4. Remarkably, the acetylation of RECQL4 by p300 in vivo leads to a significant shift of a proportion of RECQL4 protein from the nucleus to the cytoplasm. This accumulation of the acetylated RECQL4 is a result of its inability to be imported into the nucleus. Our results provide the first evidence of a post-translational modification of the RECQL4 protein, and suggest that acetylation of RECQL4 by p300 regulates the trafficking of RECQL4 between the nucleus and the cytoplasm.

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Section: Introductionmentioning

confidence: 99%

p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization

Dietschy

Shevelev

Peña-Dı́az

et al. 2009

Journal of Cell Science

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“…Ambiguities resulting from partial clinical overlap with Fanconi Anemia (FA), Werner syndrome (WS), and Dyskeratosis Congenita (DC) can be resolved by the RECQL4 test; however, this may leave open the differential diagnosis with other RECQL4-related diseases, particularly RAPADILINO syndrome. 8,9 This test should be offered to all juvenile osteosarcoma cases with poikiloderma-like lesions. Specificity:…”

Section: Diagnostic Settingmentioning

confidence: 99%

Clinical utility gene card for: Rothmund–Thomson syndrome

2012

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“…Although RAPADILINO patients share some clinical features with RTS patients, like photosensitivity with extra pigmentation of skin, or growth deficiency, there are unique diagnostic findings such as joint dislocations and patellar hypo/aplasia. In contrast to RTS, RA-DADILINO is more common in females, and only 7 % of current RAPADILINO patients carry malignant tumors, mainly osteosarcomas [16]. BGS, originally discovered in 1950 [17], is the third recently reported autosomal recessive disorder linked to mutations in the RECQL4 gene [6].…”

Section: Recql4 and Genetic Diseasesmentioning

confidence: 99%

The molecular role of the Rothmund-Thomson-, RAPADILINO- and Baller-Gerold-gene product, RECQL4: recent progress

Dietschy

Shevelev

Štagljar

2007

Cell. Mol. Life Sci.

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The RecQ family of DNA helicases is highly conserved throughout evolution and plays an important role in the maintenance of genomic stability in all organisms. Mutations in three of the five known family members in humans, BLM, WRN and RECQL4, give rise to disorders that are characterized by predisposition to cancer and premature aging, emphasizing the importance of studying the RecQ proteins and their cellular activities. Interestingly, three autosomal recessive disorders have been associated with mutations in the RECQL4 gene: Rothmund-Thomson, RAPADILINO, and Baller-Gerold syndromes, thus making RECQL4 unique within the RecQ family of DNA helicases. To date, however, the molecular function of RECQL4 and the possible cellular pathways in which it is involved remain poorly understood. Here, we present an overview of recent findings in connection with RECQL4 and try to highlight different directions the field could head, helping to clarify the role of RECQL4 in preventing tumorigenesis and maintenance of genome integrity in humans.

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A Patient With Rothmund-Thomson Syndrome and All Features of RAPADILINO

Cited by 22 publications

References 23 publications

p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization

p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization

Clinical utility gene card for: Rothmund–Thomson syndrome

The molecular role of the Rothmund-Thomson-, RAPADILINO- and Baller-Gerold-gene product, RECQL4: recent progress

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