Extreme growth failure is a common presentation of ligase IV deficiency.
Extreme growth failure is a common presentation of ligase IV deficiency.
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DOI：
10.1002/humu.22461
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发表时间：
2014-01
期刊：
影响因子：
3.9
通讯作者：
Jackson, Andrew P.
中科院分区：
文献类型：
--
作者：
Murray, Jennie E.;Bicknell, Louise S.;Yigit, Goekhan;Duker, Angela L.;van Kogelenberg, Margriet;Haghayegh, Sara;Wieczorek, Dagmar;Kayserili, Huelya;Albert, Michael H.;Wise, Carol A.;Brandon, January;Kleefstra, Tjitske;Warris, Adilia;van der Flier, Michiel;Bamforth, J. Steven;Doonanco, Kurston;Ades, Lesley;Ma, Alan;Field, Michael;Johnson, Diana;Shackley, Fiona;Firth, Helen;Woods, C. Geoffrey;Nuernberg, Peter;Gatti, Richard A.;Hurles, Matthew;Bober, Michael B.;Wollnik, Bernd;Jackson, Andrew P.
关键词：
连接酶IV综合征是一种罕见的鉴别诊断奈梅亨断裂综合征，由于共同的倾向，淋巴网状恶性肿瘤，显着小头畸形，放射超敏反应。迄今为止，仅描述了16例LIG 4突变病例，其表型从发育正常个体的恶性肿瘤到严重联合免疫缺陷和早期死亡率不等。在这里，我们报告了在11例患有小头原始侏儒症的患者中鉴定出双等位基因截短LIG 4突变，这些患者表现为产前生长受限和极端的出生后整体生长失败（平均OFC-10.1 s.d.，高度-5.1 s.d.）。随后，大多数患者在儿童期后期出现血小板减少症和白细胞减少症，许多患者在分子诊断后发现先前未被识别的免疫缺陷。尽管所有接受测试的患者都具有细胞放射敏感性，但尚未出现恶性肿瘤。基因型-表型相关性也被指出与截断突变的位置对应于疾病的严重程度。这项工作扩展了与LIG 4突变相关的表型谱，确立了极端生长迟缓伴小头畸形是双等位基因截短突变的常见表现。因此，这种生长失败足以考虑诊断为LIG 4缺陷，并且这种情况的早期识别是重要的，因为骨髓衰竭、免疫缺陷和有时恶性肿瘤是这种疾病的长期后遗症。
Ligase IV syndrome is a rare differential diagnosis for Nijmegen breakage syndrome owing to a shared predisposition to lympho-reticular malignancies, significant microcephaly, and radiation hypersensitivity. Only 16 cases with mutations in LIG4 have been described to date with phenotypes varying from malignancy in developmentally normal individuals, to severe combined immunodeficiency and early mortality. Here, we report the identification of biallelic truncating LIG4 mutations in 11 patients with microcephalic primordial dwarfism presenting with restricted prenatal growth and extreme postnatal global growth failure (average OFC −10.1 s.d., height −5.1 s.d.). Subsequently, most patients developed thrombocytopenia and leucopenia later in childhood and many were found to have previously unrecognized immunodeficiency following molecular diagnosis. None have yet developed malignancy, though all patients tested had cellular radiosensitivity. A genotype–phenotype correlation was also noted with position of truncating mutations corresponding to disease severity. This work extends the phenotypic spectrum associated with LIG4 mutations, establishing that extreme growth retardation with microcephaly is a common presentation of bilallelic truncating mutations. Such growth failure is therefore sufficient to consider a diagnosis of LIG4 deficiency and early recognition of such cases is important as bone marrow failure, immunodeficiency, and sometimes malignancy are long term sequelae of this disorder.
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DOI：
10.1016/s0921-8777(98)00063-9
发表时间：
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期刊：
MUTATION RESEARCH-DNA REPAIR
影响因子：
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作者：
Bryans, M;Valenzano, MC;Stamato, TD
通讯作者：
Stamato, TD