دورية أكاديمية
DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency
| العنوان: | DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency |
|---|---|
| المؤلفون: | Logan, C, Murray, JE, Parry, DA, Robertson, A, Bellelli, R, Tarnauskaite, Z, Challis, R, Cleal, L, Bore, V, Fluteau, A, Santoyo-Lopez, J, Aitman, T, Barroso, I, Basel, D, Bicknell, LS, Goe, H, Hu, H, Huff, C, Hutchison, M, Joyce, C, Knox, R, Lacroix, AE, Langlois, S, McCandless, S, McCarrier, J, Metcalfe, KA, Morrissey, R, Murphy, N, Netchine, I, O'connell, SM, Olney, AH, Paria, N, Rosenfeld, JA, Sherlock, M, Syverson, E, White, PC, Wise, C, Yu, Y, Zacharin, M, Banerjee, I, Reijns, M, Bober, MB, Semple, RK, Boulton, SJ, Rios, JJ, Jackson, AP |
| بيانات النشر: | CELL PRESS |
| سنة النشر: | 2018 |
| المجموعة: | The University of Melbourne: Digital Repository |
| الوصف: | During genome replication, polymerase epsilon (Pol ε) acts as the major leading-strand DNA polymerase. Here we report the identification of biallelic mutations in POLE, encoding the Pol ε catalytic subunit POLE1, in 15 individuals from 12 families. Phenotypically, these individuals had clinical features closely resembling IMAGe syndrome (intrauterine growth restriction [IUGR], metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary anomalies in males), a disorder previously associated with gain-of-function mutations in CDKN1C. POLE1-deficient individuals also exhibited distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency. All subjects shared the same intronic variant (c.1686+32C>G) as part of a common haplotype, in combination with different loss-of-function variants in trans. The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0002-9297 1537-6605 |
| العلاقة: | pii: S0002-9297(18)30400-2; Logan, C., Murray, J. E., Parry, D. A., Robertson, A., Bellelli, R., Tarnauskaite, Z., Challis, R., Cleal, L., Bore, V., Fluteau, A., Santoyo-Lopez, J., Aitman, T., Barroso, I., Basel, D., Bicknell, L. S., Goe, H., Hu, H., Huff, C., Hutchison, M. ,. Jackson, A. P. (2018). DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency. AMERICAN JOURNAL OF HUMAN GENETICS, 103 (6), pp.1038-1044. https://doi.org/10.1016/j.ajhg.2018.10.024Test.; http://hdl.handle.net/11343/250361Test |
| الإتاحة: | https://doi.org/10.1016/j.ajhg.2018.10.024Test http://hdl.handle.net/11343/250361Test |
| حقوق: | CC BY-NC-ND ; https://creativecommons.org/licenses/by-nc-nd/4.0Test |
| رقم الانضمام: | edsbas.859BA170 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00029297 15376605 |
|---|