Novel PTEN germline mutation in a family with mild phenotype: Difficulties in genetic counseling

PTEN gene (phosphatase and tensin homolog deleted on chromosome ten, MIM 601628) is a tumor suppressor gene implicated in PTEN hamartoma tumor syndromes (PHTS) including Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome and Proteus-like syndrome. PTEN mutations have been more recently reported in children with macrocephaly and autism spectrum disorders or mental retardation, without other symptoms of PHTS. Although tumor risk has not been evaluated in these patients and their relatives, the same surveillance as for Cowden syndrome is usually proposed. We report a family including patients carrying a novel PTEN mutation and presenting with a mild phenotype consisting of macrocephaly, hypotonia during the first year of life and mild learning disabilities, without autistic features. None of these patients exhibited PTHS-related symptoms such as tumors, lipomas, vascular malformations or pigmented macules of the glans penis. This report raises the question of extending the indications of PTEN mutation screening to familial macrocephaly with learning disabilities. Detection of a mutation in this family led to difficult questions about surveillance, genetic counseling and familial information since the mother declined tumor screening and disclosure of genetic risk information to at-risk relatives.     

Single nucleotide polymorphism of CD40 in the 5′-untranslated region is associated with ischemic stroke

Objectives

Ischemic stroke is influenced by both environmental and genetic factors. The CD40/CD40L system is related to proinflammatory and prothrombogenic responses, which are involved in the pathophysiology of ischemic stroke. The aim of this study was to evaluate association between the CD40 -1C/T single nucleotide polymorphism (SNP) and ischemic stroke in a Chinese population.

Methods

We conducted a case–control study including 286 ischemic stroke patients and 336 controls. CD40 -1C/T SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods, and evaluated its relevance to ischemic stroke susceptibility.

Results

Significantly increased ischemic stroke risk was found to be associated with the T allele of CD40 -1C/T (OR = 1.273, 95% CI = 1.016–1.594). The frequencies of CT and TT/CT genotypes of CD40 -1C/T in ischemic stroke patients were significantly higher than those of controls, respectively (for CT: OR = 2.350, 95% CI = 1.601–3.449; for TT/CT: OR = 2.148, 95% CI = 1.479–3.119). And, similar results were obtained after adjusting non-matched variables. We found that the frequency of carried T genotypes (TT and TT/CT) was significantly increased in patients with history of stroke compared with patients without (for TT: OR = 6.538, 95%CI = 1.655–25.833; for TT/CT: OR = 3.469, 95%CI = 1.031–11.670), respectively.

Conclusions

The findings suggested that the CD40 -1C/T polymorphism might contribute to the susceptibility to ischemic stroke in the Chinese population, and might be associated with history of previous stroke.     

Physical mapping and cloning of RAD56

Here we report the physical mapping of the rad56-1 mutation to the NAT3 gene, which encodes the catalytic subunit of the NatB N-terminal acetyltransferase in Saccharomyces cerevisiae. Mutation of RAD56 causes sensitivity to X-rays, methyl methanesulfonate, zeocin, camptothecin and hydroxyurea, but not to UV light, suggesting that N-terminal acetylation of specific DNA repair proteins is important for efficient DNA repair.     

Microsatellite markers uncover cryptic species of Odontotermes (Termitoidae: Termitidae) from Peninsular Malaysia

Termites from the genus Odontotermes are known to contain numerous species complexes that are difficult to tell apart morphologically or with mitochondrial DNA sequences. We developed markers for one such cryptic species complex, that is, Odontotermes srinakarinensis sp. nov. from Maxwell Hill Forest Reserve (Perak, Malaysia), and characterised them using a sample of 41 termite workers from three voucher samples from the same area. We then genotyped 150 termite individuals from 23 voucher samples/colonies of this species complex from several sites in Peninsular Malaysia. We analysed their population by constructing dendograms from the proportion of shared-alleles between individuals and genetic distances between colonies; additionally, we examined the Bayesian clustering pattern of their genotype data. All methods of analysis indicated that there were two distinct clusters within our data set. After the morphologies of specimens from each cluster were reexamined, we were able to separate the two species morphologically and found that a single diagnostic character found on the mandibles of its soldiers could be used to separate the two species quite accurately. The additional species in the clade was identified as Odontotermes denticulatus after it was matched to type specimens at the NHM London and Cambridge Museum of Zoology.     

Genetic associations with coronary heart disease: Meta-analyses of 12 candidate genetic variants

Aims

The aim of this study was to evaluate the combined contribution of 12 genetic variants to the risk of coronary heart disease (CHD).

Methods

Through a comprehensive literature search for genetic variants involved in the CHD association study, we harvested a total of 10 genes (12 variants) for the current meta-analyses. These genes consisted of GPX1 (rs1050450), PPARD (rs2016520), ALOX15 (rs34210653), SELPLG (rs2228315), FCGR2A (rs1801274), CCL5 (rs2107538), CYP1A1 (rs4646903), TP53 (rs1042522), CX37 (rs1764391), and PECAM1 (rs668, rs12953, and rs1131012).

Results

A total of 45 studies among 23,314 cases and 28,430 controls were retrieved for the meta-analyses of 12 genetic variants. The results showed a significant association between the GPX1 rs1050450 polymorphism and CHD (odd ratio (OR) = 1.61, 95% confidence interval (CI) = 1.25–2.07, P = 0.0002). Other meta-analyses of the rest 11 variants suggested a lack of association with the risk of CHD.

Conclusion

Our results confirmed that GPX1 rs1050450 was associated with susceptibility to CHD in Chinese and Indian populations.     

Association between interleukin-10 promoter polymorphisms and endometriosis: A meta-analysis

To investigate the influence of the interleukin-10 gene promoter polymorphisms on the susceptibility of endometriosis, we examined the association by performing a meta-analysis. The PubMed, Embase, HuGE Navigator and CNKI were searched to identify eligible studies. We then conducted a meta-analysis to examine the association between interleukin-10 gene promoter polymorphisms and endometriosis. Eight case–control studies which examined the association between the IL-10 gene promoter polymorphisms and the susceptibility to endometriosis were finally included in the meta-analysis. Meta-analysis of the IL-10 − 592 A/C polymorphisms showed a significant increased risk of endometriosis in the overall and Asian population in all genetic models and allele contrast. However, meta-analysis of the IL-10 − 1082 A/G and IL-10 − 819 T/C polymorphisms showed no association with endometriosis in all genetic models and allele contrast in the overall and Asian population samples. In addition, there was not a significant association between the IL-10 − 592 A/C gene promoter polymorphisms with the severity of endometriosis.     

The natural place to begin: The ethnoprimatology of the Waorani

Ethnoprimatology is an important and growing discipline, studying the diverse relationships between humans and primates. However there is a danger that too great a focus on primates as important to humans may obscure the importance of other animal groups to local people. The Waorani of Amazonian Ecuador were described by Sponsel [Sponsel (1997) New World Primates: Ecology, evolution and behavior. New York: Aldine de Gruyter. p 143–165] as the “natural place” for ethnoprimatology, because of their close relationship to primates, including primates forming a substantial part of their diet. Therefore they are an ideal group in which to examine contemporary perceptions of primates in comparison to other types of animal. We examine how Waorani living in Yasuní National Park name and categorize primates and other common mammals. Although there is some evidence that the Waorani consider primates a unique group, the non‐primate kinkajou and olingo are also included as part of the group “monkeys,” and no evidence was found that primates were more important than other mammals to Waorani culture. Instead, a small number of key species, in particular the woolly monkey (Lagothrix poeppigii) and white‐lipped peccary (Tayassu pecari), were found to be both important in the diet and highly culturally salient. These results have implications for both ethnoprimatologists and those working with local communities towards broader conservation goals. Firstly, researchers should ensure that they and local communities are referring to the same animals when they use broad terms such as “monkey,” and secondly the results caution ethnoprimatologists against imposing western taxonomic groups on indigenous peoples, rather than allowing them to define themselves which species are important. Am. J. Primatol. 75:1117–1128, 2013. © 2013 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc.