Background Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice. Methods The genes known to cause CMT were sequenced in 1607 patients with CMT (425 patients attending an inherited neuropathy clinic and 1182 patients whose DNA was sent to the authors for genetic testing) to determine the proportion of different subtypes in a UK population. Results A molecular diagnosis was achieved in 62.6% of patients with CMT attending the inherited neuropathy clinic; in 80.4% of patients with CMT1 (demyelinating CMT) and in 25.2% of those with CMT2 (axonal CMT). Mutations or rearrangements in PMP22, GJB1, MPZ and MFN2 accounted for over 90% of the molecular diagnoses while mutations in all other genes tested were rare. Conclusion Four commonly available genes account for over 90% of all CMT molecular diagnoses; a diagnostic algorithm is proposed based on these results for use in clinical practice. Any patient with CMT without a mutation in these four genes or with an unusual phenotype should be considered for referral for an expert opinion to maximize the chance of reaching a molecular diagnosis.

Research into proximate and ultimate mechanisms of individual cognitive variation in animal populations is a rapidly growing field that incorporates physiological, behavioural and evolutionary investigations. Recent studies in humans and laboratory animals have shown that the enteric microbial community plays a central role in brain function and development. The 'gut-brain axis' represents a multi-directional signalling system that encompasses neurological, immunological and hormonal pathways. In particular it is tightly linked with the hypothalamic-pituitary-adrenal axis (HPA), a system that regulates stress hormone release and influences brain development and function. Experimental examination of the microbiome through manipulation of diet, infection, stress and exercise, suggests direct effects on cognition, including learning and memory. However, our understanding of these processes in natural populations is extremely limited. Here, we outline how recent advances in predominantly laboratory-based microbiome research can be applied to understanding individual differences in cognition. Experimental manipulation of the microbiome across natal and adult environments will help to unravel the interplay between cognitive variation and the gut microbial community. Focus on individual variation in the gut microbiome and cognition in natural populations will reveal new insight into the environmental and evolutionary constraints that drive individual cognitive variation.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.

The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.

Cognition arguably drives most behaviours in animals, but whether and why individuals in the wild vary consistently in their cognitive performance is scarcely known, especially under mixed-species scenarios. One reason for this is that quantifying the relative importance of individual, contextual, ecological and social factors remains a major challenge. We examined how many of these factors, and sources of bias, affected participation and performance, in an initial discrimination learning experiment and two reversal learning experiments during self-administered trials in a population of great tits and blue tits. Individuals were randomly allocated to different rewarding feeders within an array. Participation was high and only weakly affected by age and species. In the initial learning experiment, great tits learned faster than blue tits. Great tits also showed greater consistency in performance across two reversal learning experiments. Individuals assigned to the feeders on the edge of the array learned faster. More errors were made on feeders neighbouring the rewarded feeder and on feeders that had been rewarded in the previous experiment. Our estimates of learning consistency were unaffected by multiple factors, suggesting that, even though there was some influence of these factors on performance, we obtained a robust measure of discrimination learning in the wild.

Attending to where others are looking is thought to be of great adaptive benefit for animals when avoiding predators and interacting with group members. Many animals have been reported to respond to the gaze of others, by co-orienting their gaze with group members (gaze following) and/or responding fearfully to the gaze of predators or competitors (i.e., gaze aversion). Much of the literature has focused on the cognitive underpinnings of gaze sensitivity, namely whether animals have an understanding of the attention and visual perspectives in others. Yet there remain several unanswered questions regarding how animals learn to follow or avoid gaze and how experience may influence their behavioral responses. Many studies on the ontogeny of gaze sensitivity have shed light on how and when gaze abilities emerge and change across development, indicating the necessity to explore gaze sensitivity when animals are exposed to additional information from their environment as adults. Gaze aversion may be dependent upon experience and proximity to different predator types, other cues of predation risk, and the salience of gaze cues. Gaze following in the context of information transfer within social groups may also be dependent upon experience with group-members; therefore we propose novel means to explore the degree to which animals respond to gaze in a flexible manner, namely by inhibiting or enhancing gaze following responses. We hope this review will stimulate gaze sensitivity research to expand beyond the narrow scope of investigating underlying cognitive mechanisms, and to explore how gaze cues may function to communicate information other than attention.

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The hereditary sensory and autonomic neuropathies (HSAN) are rare inherited neuropathies presenting with sensory loss and complications, including ulcers, infections, osteomyelitis and amputations. Usually, sensory symptoms predominate although motor involvement can occur. Autonomic features may be minimal (then hereditary sensory neuropathy, HSN, is preferred). HSAN has been classified into five subtypes depending on clinical presentation.1 Hereditary sensory and autonomic neuropathy II (HSANII or HSNII) is an early onset, autosomal recessive sensory neuropathy with ulcero-mutilating complications due to mutations in the HSN2 isoform of the WNK1 gene.2 Recently, a similar phenotype was described in a Saudi-Arabian family, and a homozygous nonsense mutation found in a new gene, FAM134B (family with sequence similarity 134, member B), encoding a newly identified Golgi protein. The index case in this family was initially thought to have leprosy. Three additional families (out of 75 patients) with similar phenotypes were found to have homozygous loss of function mutations in FAM134B.3 Here, we report the clinical and pathological findings in a further patient with HSNII due to a homozygous mutation in FAM134B.