DNA ligase IV functions in DNA nonhomologous end-joining and V(D)J recombination. Four patients with features including immunodeficiency and developmental and growth delay were found to have mutations in the gene encoding DNA ligase IV (LIG4). Their clinical phenotype closely resembles the DNA damage response disorder, Nijmegen breakage syndrome (NBS). Some of the mutations identified in the patients directly disrupt the ligase domain while others impair the interaction between DNA ligase IV and Xrcc-4. Cell lines from the patients show pronounced radiosensitivity. Unlike NBS cell lines, they show normal cell cycle checkpoint responses but impaired DNA double-strand break rejoining. An unexpected V(D)J recombination phenotype is observed involving a small decrease in rejoining frequency coupled with elevated imprecision at signal junctions.

No abstract

No abstract

Summary In this study the saturated and aromatic hydrocarbon fractions of a marl sample from a Messinian (late Micoene) evaporitic basin located in the northern Apennines, and four oils, Rozel Point oil (Utah, USA; Miocene) and three seep oils from Sicily (Messinian), have been studied by GC with simultaneous FID and FPD detection and by GC-MS. All samples show characteristics which might be linked to hypersaline conditions prevailing during the time of deposition. Some of these characteristics are: a very low pristane/phytane ratio (<0.1), a relatively high abundance of docosane (C 22 ) and gammacerane and a series of extended hopanes and/or hop-17(21)-enes maximizing at C 35 . The aromatic hydrocarbon fraction of all samples is dominated by organic sulphur compounds of which 2,3-dimethyl-5-(2,6,10-trimethylundecyl) thiophene is the most abundant compound. The suggestion of Meissner et al. (1984), that the source rock of Rozel Point oil was deposited under hypersaline conditions in a playa-like system, is supported by the organic geochemical characteristics of this oil.

The Adams-Oliver syndrome (AOS) is defined as aplasia cutis congenita (ACC) with transverse terminal limb defects (TTLD). Frequencies of associated anomalies are not well characterized. Six causative genes have been identified: ARHGAP31, DOCK6, EOGT, RBPJ, NOTCH1, and DLL4. We review 385 previously described individuals (139 non-familial and 246 familial probands and family members) and add clinical data on 13 previously unreported individuals with AOS. In addition to ACC and TTLD, the most commonly associated anomalies included a wide variety of central nervous system (CNS) anomalies and congenital heart defects each seen in 23%. CNS anomalies included structural anomalies, microcephaly, vascular defects, and vascular sequelae. CNS migration defects were common. Cutis marmorata telangiectasia congenita (CMTC) was found in 19% of the study population and other vascular anomalies were seen in 14%. Hemorrhage was listed as the cause of death for five of 25 deaths reported. A relatively large number of non-familial probands were reported to have hepatoportal sclerosis with portal hypertension and esophageal varices. Non-familial probands were more likely to have additional anomalies than were familial probands. The data reported herein provide a basis for refining the diagnostic features of AOS and suggest management recommendations for probands newly diagnosed with AOS. © 2017 Wiley Periodicals, Inc.