Glycogen storage disease type 1a in Israel: Biochemical,clinical, and mutational studies

Glycogen storage disease type 1a (von Gierke disease, GSD 1a) is caused by the deficiency of microsomal glucose-6-phosphatase (G6Pase) activity which catalyzes the final common step of glycogenolysis and gluconeogenesis. The recent cloning of the G6Pase cDNA and characterization of the human G6Pase gene enabled the characterization of the mutations causing GSD 1a. This, in turn, allows the introduction of a noninvasive DNA-based diagnosis that provides reliable carrier testing and prenatal diagnosis. In this study, we report the biochemical and clinical characteristics as well as mutational analyses of 12 Israeli GSD 1a patients of different families, who represent most GSD 1a patients in Israel. The mutations, G6Pase activity, and glycogen content of 7 of these patients were reported previously. The biochemical data and clinical findings of all patients were similar and compatible with those described in other reports. All 9 Jewish patients, as well as one Muslim Arab patient, presented the R83C mutation. Two Muslim Arab patients had the V166G mutation which was not found in other patients' populations. The V166G mutation, which was introduced into the G6Pase cDNA by site-directed mutagenesis following transient expression in COS-1 cells, was shown to cause complete inactivation of the G6Pase. The characterization of all GSD 1a mutations in the Israeli population lends itself to carrier testing in these families as well as to prenatal diagnosis, which was carried out in 2 families. Since all Ashkenazi Jewish patients harbor the same mutation, our study suggests that DNA-based diagnosis may be used as an initial diagnostic step in Ashkenazi Jews suspected of having GSD 1a, thereby avoiding liver biopsy. Am. J. Med. Genet. 72:286–290, 1997. © 1997 Wiley-Liss, Inc.     

Mothers' marital adaptation following the birth of twins or singletons: empirical evidence and practical insights

Parenting twins is typically portrayed as more stressful than is parenting single children and, therefore, more of a strain on the marital relationship. With this in mind, the present study examined the contribution of infant characteristics and mother's internal resources (attachment style) and external resources (maternal and paternal grandmothers' perceived support) to their marital adaptation during the first month following delivery, comparing mothers of twins (n = 88) with mothers of singletons (n = 82). The findings indicate that both internal and external resources contribute to the marital adaptation of the two groups, even beyond the contribution of specific circumstances. Thus, it seems that the birth of twins and the birth of a single child are normative life events that have more in common than previously acknowledged. The implications for the focus of social work interventions, particularly in the case of the birth of twins, are discussed.     

Immune deficiency augments the prevalence of p53 loss of heterozygosity in spontaneous tumors but not bi‐directional loss of heterozygosity in bone marrow progenitors

p53 loss of heterozygosity (LOH) is a frequent event in tumors of somatic and Li‐Fraumeni syndrome patients harboring p53 mutation. Here, we focused on resolving a possible crosstalk between the immune‐system and p53 LOH. Previously, we reported that p53 heterozygous bone‐marrow mesenchymal progenitor cells undergo p53 LOH in‐vivo. Surprisingly, the loss of either the wild‐type p53 allele or mutant p53 allele was detected with a three‐to‐one ratio in favor of losing the mutant allele. In this study, we examined whether the immune‐system can affect the LOH directionality in bone marrow progenitors. We found that mesenchymal progenitor cells derived from immune‐deficient mice exhibited the same preference of losing the mutant p53 allele as immune‐competent matched cells, nevertheless, these animals showed a significantly shorter tumor‐free survival, indicating the possible involvement of immune surveillance in this model. Surprisingly, spontaneous tumors of p53 heterozygous immune‐deficient mice exhibited a significantly higher incidence of p53 LOH compared to that observed in tumors derived of p53 heterozygous immune‐competent mice. These findings indicate that the immune‐system may affect the p53 LOH prevalence in spontaneous tumors. Thus suggesting that the immune‐system may recognize and clear cells that underwent p53 LOH, whereas in immune‐compromised mice, those cells will form tumors with shorter latency. In individuals with a competent immune‐system, p53 LOH independent pathways may induce malignant transformation which requires a longer tumor latency. Moreover, this data may imply that the current immunotherapy treatment aimed at abrogating the inhibition of cellular immune checkpoints may be beneficial for LFS patients.