暂无摘要。

UNASSIGNED: Premarital screening (PMS) is an essential global measure that seeks to reduce the occurrence of specific genetic disorders and sexually transmitted diseases common in consanguineous marriages. Due to the lack of a nationwide study, this research was designed to comprehend how unmarried individuals perceive the risks and benefits of PMS.
UNASSIGNED: A cross-sectional study was conducted using an online questionnaire distributed through different social media platforms, responses from the native adult population (18-49 years) Saudi Arabia was only included in the study. The questionnaire was based on the Health Belief Model (HBM) to assessing seven different constructs including susceptibility, seriousness, benefits-, barriers-, & cues- to action, self-efficacy, and social acceptance. Data frequency was represented by mean and standard deviation; chi-square and t-tests were conducted for the comparison of independent and dependent variables. A multinomial logistic regression was used to predict factors influencing decisions related to PMS.
UNASSIGNED: 1,522 participants completed the survey, mostly 18-25 years old and most of them were women. The majority were single with 85 men and 1,370 women. Most participants (59.6%) believed their parents were related, while 40.5% did not. 122 respondents reported they had to marry within their tribe. Findings revealed significant correlations among all HBM themes, with varying strengths. Notably, a moderate positive relationship was found between the perception of benefits and cues to action, suggesting that enhancing the perceived benefits of PMS could facilitate safe marriage practices. Multinomial regression analysis revealed that demographic factors and health beliefs significantly influence individuals\' intentions and behaviors toward PMS and safe marriage.
UNASSIGNED: The study concludes that by identifying and addressing barriers, and promoting positive social acceptance, PMS can significantly contribute to preventing genetic diseases and promoting safe marriage practices, although the cross-sectional design limits the establishment of causal relationships and further research is needed.

Duodenopancreatic neuroendocrine neoplasia (DP-NEN) is in approximately 10% of cases of multiple endocrine neoplasia type 1 (MEN1). We encountered a case in which the onset of NEN led to suspicion and diagnosis of MEN1. Although genetic testing showed MEN1 variant of uncertain significance (VUS), we considered it pathological from the clinical course, promoting the provision of genetic counseling and screening for relatives. MEN1 has a variety of clinical manifestations, and DP-NENs are the second-most common manifestation after primary hyperparathyroidism (pHPT). It is important to assume that MEN1 is an underlying cause of NEN.

BACKGROUND: Germline mutations in CDKN2A result in Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM) (OMIM #155,601), which is associated with an increased risk of pancreatic ductal adenocarcinoma and melanoma. FAMMM has been reported globally, but it is quite rare in Japan. We report two families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A that were incidentally identified through comprehensive genomic profiling.
METHODS: The first case is a 74-year-old woman with a diagnosis of pancreatic carcinoma with multiple liver metastases. She had family histories of pancreatic cancer, but no personal or family history of malignant melanoma. Whole exon sequencing detected a germline CDKN2A variant evaluated as likely pathogenic. The results were disclosed to her daughters after she died, and the same CDKN2A variant was detected in one of the daughter. The daughter was referred to a nearby hospital for her clinical management. The second case is a 65-year-old man with pancreatic ductal adenocarcinoma. He had family histories of pancreatic cancer, but no personal or family history of malignant melanoma. He underwent a comprehensive genomic profiling test using pancreatic cancer tissue, and detected a presumed germline pathogenic variant of CDKN2A. Germline testing confirmed the same CDKN2A variant. Genetic analysis of his relatives produced negative results. Other blood relatives are scheduled for genetic analysis in the future. We report two families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A that were incidentally identified through comprehensive genomic profiling.
CONCLUSIONS: In current Japanese precision medicine, comprehensive genetic analysis can reveal rare genetic syndromes and offer us the opportunity to provide health management for patients and their relatives. However, gene-specific issues are raised in terms of the evaluation of a variant\'s pathogenicity and the extent of surveillance of the at-risk organs due to a lack of genetic and clinical data concerning CDKN2A variant carriers in Japan.

Although the presence of companion(s) in a genetic counseling session can positively influence session dynamics, research has found that some patients prefer to attend their appointments alone. To date, no studies have examined patient accompaniment preferences across different cultural groups in the context of genetic counseling. This quantitative study aimed to identify factors associated with individual preferences in accompaniment at cancer genetic counseling appointments in a sample (N = 130) of Hispanic/Latine (n = 29) and non-Hispanic/Latine White (n = 101) participants at a large academic medical institution. Variables examined included demographics, horizontal and vertical collectivism, and Hispanic and American acculturation. A link to an online questionnaire was emailed to patients who met four criteria: (1) identified as either Hispanic/Latine or non-Hispanic/Latine White; (2) had attended a cancer genetic counseling appointment at UCLA Health to discuss genetic testing options between October 2020 and December 2022; (3) were at least 18 years of age at the time of their appointment; and (4) indicated they were comfortable reading in Spanish or English; responses were anonymous. Logistic regression analyses identified four significant variables in the model associated with accompaniment preferences: individuals with at least one parent born outside of the US, those who attended their appointment in-person, and those with a higher horizontal collectivism score were less likely to want to attend their cancer genetic counseling appointment alone, while the converse was true among those with a higher American acculturation score. These findings highlight cultural and demographic factors that are associated with patient accompaniment preferences unrelated to ethnicity, indicating genetic counselors should not make assumptions regarding accompaniment preferences based solely on cultural or racial/ethnic background. Genetic counselors should incorporate this understanding when assessing patients\' accompaniment preferences.

BACKGROUND: Shortened telomere length (TL) is a genomic risk factor for fibrotic interstitial lung disease (ILD), but its role in clinical management is unknown.
OBJECTIVE: What is the clinical impact of TL testing on the management of ILD?
METHODS: Patients were evaluated in the Columbia University ILD clinic and underwent CLIA-certified TL testing by flow cytometry and fluorescence in-situ hybridization (FlowFISH) as part of clinical management. Short TL was defined as below the 10th age-adjusted percentile for either granulocytes or lymphocytes by FlowFISH. Patients were offered genetic counseling and testing if they had short TL or a family history of ILD. FlowFISH TL was compared against research qPCR TL measurement.
RESULTS: A total of 108 patients underwent TL testing, including those with clinical features of short telomere syndrome such as familial pulmonary fibrosis (50%) or extrapulmonary manifestations in the patient (25%) or a relative (41%). The overall prevalence of short TL was 46% and was similar across clinical ILD diagnoses. The number of short telomere clinical features was independently associated with detecting short TL (OR 2.00, 95% CI [1.27, 3.32]). TL testing led to clinical management changes for 35 (32%) patients, most commonly resulting in reduction or avoidance of immunosuppression. Of the patients who underwent genetic testing (n=34), a positive or candidate diagnostic finding in telomere-related genes was identified in 10 (29%) patients. Inclusion of TL testing below the 1st percentile helped reclassify 8 of 9 variants of uncertain significance (VUS) into actionable findings. The qPCR test correlated with FlowFISH, but age-adjusted percentile cutoffs may not be equivalent between the two assays.
CONCLUSIONS: Incorporating TL testing in ILD impacted clinical management and led to the discovery of new actionable genetic variants.

Fragile X syndrome is the most commonly inherited form of intellectual disability. Identifying fragile X syndrome at a young age can be quite challenging because the classical physical features usually present in late childhood or early adolescence; therefore, it is important to consider genetic testing for all males with unexplained developmental delays, intellectual disability, and autism, females with developmental delays, intellectual disability or autism, and a family history of fragile X gene disorders. There is no specific treatment to manage fragile X syndrome. Still, a prompt referral for early intervention is essential to help maximize the child\'s learning potential, as well as a referral to child psychology if any behavioral concerns are present. It is of paramount importance for families with a history of fragile X syndrome to have access to genetic counseling as it can aid in future reproductive decisions and the risk of future recurrences of this condition. [Pediatr Ann. 2024;53(7):e269-e271.].

Heterozygous Familial Hypercholesterolemia (HeFH) is an autosomal dominant disorder causing elevated low density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. Universal cholesterol screening in childhood leads to children serving as the index case for their family, but efficacy of cascade screening and genetic counseling in this population is not well understood. The institutional pediatric lipid clinic database was queried from 2011 to 2022 for subjects <18 years who met clinical HeFH diagnostic criteria (N = 256). Median peak LDL-C was 198 mg/dL (IQR 179-238 mg/dL) and 69.5 % of subjects were the index case. The number of new HeFH cases identified per index case was 3.55 ± 1.87. Genetic counseling was offered to 38.7 % of subjects and genetic testing was completed by 10.9 %, 53.6 % of whom had a pathogenic or likely pathogenic genetic variant for HeFH. Our findings highlight the effectiveness of cascade screening from pediatric index cases identified through universal screening. However, genetic counseling and genetic testing may be underutilized in this population.

Since its debut in 2011, Non-Invasive Prenatal Testing (NIPT) has continually demonstrated its effectiveness in detecting an expanding number of diseases. NIPT offers a less invasive approach to prenatal chromosomal disease screening, providing prospective parents with vital information to better prepare for their potential pregnancy outcomes. NIPT was primarily designed for screening trisomy 13, 18, and 21. However, its scope has since broadened to encompass microdeletions and autosomal dominant monogenic diseases. Conversely, the normalization of NIPT can have unintended consequences. Some patients opt for NIPT without any medical indications, driven by a desire to remain cautious. This over-screening for chromosomal abnormalities can exacerbate pregnancy-related anxiety, as individuals might feel pressured into taking the test unnecessarily. While NIPT can be highly successful when conducted correctly, it is not infallible, and obstetricians play a crucial role in managing patient expectations. This includes providing genetic counseling to individuals with relevant genetic information regarding their personal and family histories. In the context of NIPT, a bioinformatics analysis is performed on a cell-free DNA (cfDNA) sample extracted from the mother\'s placenta to determine the fetal fraction (FF). This FF measurement is vital for quality control and ensuring statistical confidence in the test results. Raising awareness among clinicians about the significance of FF enhances patient care and alleviate concerns about the possibility of failed NIPT. This paper aims to explore the ongoing debates and more specifically the significance and pitfalls of NIPT on a psychosocial and ethical scale, all while highlighting the importance of genetic counseling.

UNASSIGNED: Little evidence is available on the disease expression in relatives of index patients with hypertrophic cardiomyopathy (HCM). This information has important implications for family screening programs, genetic counseling, and management of affected families.
UNASSIGNED: The purpose of this study was to investigate the disease expression and penetrance in relatives of index patients carrying pathogenic/likely pathogenic (P/LP) variants in recognized HCM genes.
UNASSIGNED: A total of 453 consecutive and unrelated HCM index patients underwent clinical and genetic investigations. A total of 903 relatives of genotype-positive index patients were invited for clinical investigations and genetic testing. Penetrance, disease expression, and incidence rates of major adverse cardiac events (MACEs) were investigated in individuals carrying P/LP variants.
UNASSIGNED: Forty percent (183/453) of index patients carried a P/LP variant. Eighty-four percent (757/903) of all relatives of index patients with P/LP variants were available for the investigation, of whom 54% (407/757) carried a P/LP variant. The penetrance of HCM among relatives was 39% (160/407). Relatives with HCM and index patients were diagnosed at a similar age (43 ± 18 years vs 46 ± 15 years; P = 0.11). There were no differences in clinical characteristics or incidence rates of MACE during 8 years of follow-up.
UNASSIGNED: The disease expression of HCM among index patients and affected relatives carrying P/LP variants in recognized disease genes was similar, with an equal risk of experiencing MACE. These findings provide evidence to support family screening and follow-up of genotype-positive HCM families to improve management and diminish the number of adverse disease complications among relatives.