Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype–phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot–Marie–Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.

The genetic counseling profession is continuing to develop globally, with countries in various stages of development. In some, the profession has been in existence for decades and is increasingly recognized as an important provider of allied health, while in others it is just beginning. In this article, we describe the current global landscape of the genetic counseling specialty field's professional development. Using examples of the United States, United Kingdom, Canada, Australia, South Africa, and various countries in Asia, we highlight the following: (a) status of genetic counseling training programs, (b) availability of credentialing through government and professional bodies (certification, registration, and licensure), and potential for international reciprocity, (c) scope of clinical practice, and (d) health‐care system disparities and cultural differences impacting on practice. The successful global implementation of precision medicine will require both an increased awareness of the importance of the profession of “genetic counselor” and flexibility in how genetic counselors are incorporated into each country's health‐care market. In turn, this will require more collaboration within and across nations, along with continuing engagement of existing genetic counseling professional societies.

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BACKGROUND Lynch syndrome confers a hereditary predisposition to colorectal and other cancers. Universal tumor screening (UTS) for Lynch syndrome is recommended by several professional societies, but implementation can be complex. We describe the evaluation, process development, and initiation of Lynch syndrome UTS at our institution, a tertiary referral cancer center. METHODS A multidisciplinary team developed the new process design. Issues in five themes were noted: timing, funding, second opinion patients, result processing, and the role of genetics providers. A committee approach was used to examine each issue for process improvement development. RESULTS The issues related to testing were addressed individually for successful implementation of UTS at the institutional level. In the “conventional care” period, 9/30 (30%) cases received Lynch syndrome screening and four cases were referred to medical genetics. During the six months following implementation of “UTS,” 32/44 (73%) patients received Lynch syndrome screening. The 12 unscreened patients all had identified reasons for non-screening (e.g. financial limitations). Ten patients were referred to medical genetics, from which no new cases of Lynch syndrome were identified, but a low-risk APC variant was detected in one individual. CONCLUSIONS Implementation of effective Lynch syndrome UTS can feasibly alter practice at the institutional level. Our experience with the assessment and management of issues relevant to successful implementation of a new clinical care paradigm based on emerging technology has implications for the uptake of advances across molecular oncology into clinical practice, which is highly relevant in the current era of rapidly evolving genomics technology.