RESUMEN
Li-Fraumeni syndrome (LFS) is an inherited, autosomal-dominant condition that predisposes individuals to a wide-spectrum of tumors at an early age. Approximately 70% of families with classic LFS have pathogenic variants in the tumor suppressor gene TP53 that disrupt protein function or stability. While more than 70% of pathogenic variants in TP53 are missense variants, the vast majority occur very infrequently, and thus their clinical significance is uncertain or conflicting. Here, we report an extremely rare TP53 missense variant, c.799C > T (p.Arg267Trp), identified in a 2-year-old Saudi proband diagnosed with choroid plexus carcinoma (CPC) and six of his first- and second-degree relatives. CPC is frequently found in families with LFS, and this is the first detailed report of a family with this variant. Intriguingly, the proband's father is homozygous for TP53 c.799C > T and phenotypically normal at 39 years of age. While loss of TP53 heterozygosity is often observed in tumors from individuals with LFS, homozygous germline TP53 pathogenic variants are rare. Based on our analysis of this single family, we hypothesize that TP53 c.799C > T has low or variable penetrance for LFS, with predisposition to the development of CPC. The observations from this family have furthered our understanding of the phenotypic variability that may be caused by one variant of TP53, even in the same family, and suggest that other factors (genetic and/or environmental) may play a role in mechanism of disease manifestation in LFS.
RESUMEN
BACKGROUND: Helicobacter pylori is a common gut pathogen that is linked to many complications of pregnancy such as iron deficiency anemia, pre-eclampsia and thrombocytopenia. There are no published data on H. pylori in Sudan. METHODS: A cross-sectional study was conducted during the period May-June 2012 at the antenatal care unit of Khartoum Hospital, Sudan, to investigate prevalence of H. pylori and its association, if any, with anemia and thrombocytopenia. Obstetric and medical histories were gathered using questionnaires. Hemoglobin and serum ferritin were measured and H. pylori antibodies (IgA and IgG) investigated using ELISA. RESULTS: Among 179 women, rates of positivity for specific IgG formed against H. pylori were 69.8% (125/179), 94.0% (168/179) and 5.6% (10/179) for IgA, IgG and both IgG and IgA, respectively. There was no association between the expected risk factors (age, parity, education) and H. pylori seropositivity. Of these women, 42/179 (24.3%), 50/179 (28.9%) and 19/179 (11%), respectively, were anemic (hemoglobin <11 g/dl) or had iron deficiency (serum ferritin <15 µg/l) or iron deficiency anemia. There was no association between H. pylori infection and anemia (OR=1.0, 95% CI=0.3-3.2, p=1.0), iron deficiency (OR=0.6, 95% CI=0.1-3.8, p=0.367) or thrombocytopenia (OR=2.0, 95% CI=0.4-8.4, p=0.322). CONCLUSION: There is a high prevalence of H. pylori infection among pregnant women in Khartoum, Sudan, and it is not associated with anemia or thrombocytopenia.