Risk assessment and genetic counseling for Lynch syndrome - Practice resource of the National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer.

Identifying individuals who have Lynch syndrome involves a complex diagnostic workup that includes taking a detailed family history and a combination of various tests such as immunohistochemistry and/or molecular which may be germline and/or somatic. The National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer have come together to publish this practice resource for the evaluation of Lynch syndrome. The purpose of this practice resource was to provide guidance and a testing algorithm for Lynch syndrome as well as recommendations on when to offer testing. This practice resource does not replace a consultation with a genetics professional. This practice resource includes explanations in support of this and a summary of background data. While this practice resource is not intended to serve as a review of Lynch syndrome, it includes a discussion of background information and cites a number of key publications which should be reviewed for a more in-depth understanding. This practice resource is intended for genetic counselors, geneticists, gastroenterologists, surgeons, medical oncologists, obstetricians and gynecologists, nurses, and other healthcare providers who evaluate patients for Lynch syndrome.

Discovery of the BMPR1A promoter and germline mutations that cause juvenile polyposis.

Juvenile polyposis (JP) is an autosomal dominant hamartomatous polyposis syndrome where affected individuals are predisposed to colorectal and upper gastrointestinal cancer. Forty-five percent of JP patients have mutations or deletions involving the coding regions of SMAD4 and BMPR1A, but the genetic basis of other cases is unknown. We set out to identify the JP gene in a large kindred having 10 affected members without SMAD4 or BMPR1A coding sequence mutations or deletions. We found a germline deletion segregating in all affected members, mapping 119 kb upstream of the coding region of BMPR1A by multiplex ligation-dependent probe amplification and comparative genomic hybridization. To further understand the genomic structure of BMPR1A, we performed 5' RACE from lymphoblastoid cell lines and normal colon tissue, which revealed four non-coding (NC) exons and two putative promoters. Further analysis of this deletion showed that it encompassed 12 433 bp, including one promoter and NC exon. The activities of each promoter and deletion constructs were evaluated by luciferase assays, and the stronger promoter sequence analyzed for changes in JP patients without SMAD4 or BMPR1A alterations. A total of 6 of 65 JP probands were found to have mutations affecting this promoter. All probands examined had diminished BMPR1A protein by ELISA, and all promoter mutations but one led to significantly reduced luciferase activity relative to the wild-type promoter reporter. We conclude that we have identified the promoter for BMPR1A, in which mutations may be responsible for as many as 10% of JP cases with unknown mutations.

A Case for Inclusion of Genetic Counselors in Cardiac Care.

Recent advances in genetic testing for heritable cardiac diseases have led to an increasing involvement of the genetic counselor in cardiology practice. We present a series of cases collected from a nationwide query of genetics professionals regarding issues related to cost and utilization of genetic testing. Three themes emerged across cases: (1) choosing the most appropriate genetic test, (2) choosing the best person to test, and (3) interpreting results accurately. These cases demonstrate that involvement of a genetic counselor throughout the evaluation, diagnosis, and continuing management of individuals and families with inherited cardiovascular conditions helps to promote the efficient use of healthcare dollars.

Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.

These cancer genetic counseling recommendations describe the medical, psychosocial, and ethical ramifications of identifying at-risk individuals through cancer risk assessment with or without genetic testing. They were developed by members of the Practice Issues Subcommittee of the National Society of Genetic Counselors Cancer Genetic Counseling Special Interest Group. The information contained in this document is derived from extensive review of the current literature on cancer genetic risk assessment and counseling as well as the personal expertise of genetic counselors specializing in cancer genetics. The recommendations are intended to provide information about the process of genetic counseling and risk assessment for hereditary cancer disorders rather than specific information about individual syndromes. Key components include the intake (medical and family histories), psychosocial assessment (assessment of risk perception), cancer risk assessment (determination and communication of risk), molecular testing for hereditary cancer syndromes (regulations, informed consent, and counseling process), and follow-up considerations. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a client.