Latest news with #genetic testing
Medscape
2 days ago
- Health
- Medscape
Testing for LMNA Mutations Called ‘Woefully Underutilized'
People with mutated copies of the LMNA gene are at high risk for cardiac laminopathies, including atrioventricular block and atrial or ventricular arrhythmias (VAs) leading to dilated cardiomyopathy. These autosomal dominant mutations have a high penetrance, meaning that a high percentage of persons with a pathogenic or likely pathogenic variant will develop health problems related to the gene. For those with cardiac manifestations, about 90% of carriers of LMNA mutations older than 30 years have a high risk for sudden death from arrhythmia — even patients with minimal left ventricular dilation and mild systolic impairment — well before the onset of heart failure. A long-term follow-up study from 122 consecutive carriers of LMNA mutations with cardiac conditions showed that most had experienced arrhythmia, heart block, embolic events, or heart failure within 7 years of diagnosis. Could some outcomes, such as sudden cardiac death, be averted with a more precise view of LMNA mutations? New research published in JAMA Cardiology shows pinpointing the type and location of the LMNA mutation may guide clinicians toward earlier treatment approaches to improve prognosis for these high-risk patients. These interventions might include earlier placement of implantable cardioverter-defibrillator (ICD) devices and family testing to detect the mutation before the onset of symptoms. 'Genetic testing for dilated cardiomyopathy is woefully underutilized,' said the paper's senior author, Neal Lakdawala, MD, an associate professor of medicine at Harvard Medical School and a cardiologist in the Heart and Vascular Center at Brigham and Women's Hospital, in Boston. In fact, claims data showed that fewer than 2% of patients with dilated cardiomyopathy undergo genetic testing. 'Prior research has established the prognostic power of a genetic diagnosis,' Lakdawala told Medscape Medical News . 'We took it one step further within a specific genetic etiology, to show that the type of gene variant and the location of a gene variant also matter.' The retrospective cohort study examined international registry data from 718 patients (mean age, 41.3 ± 14.3 years) with pathogenic or likely pathogenic variants of LMNA . The participants in the study had no prior history of malignant VA. The primary outcome was time to malignant VA, defined as sudden cardiac death, placement of an ICD, or other manifestations of hemodynamically unstable VA. The secondary outcome, advanced heart failure, was defined as nonsudden cardiac death, implantation of a left ventricular assist device, or heart transplant. Reflecting the high risk associated with LMNA mutations, Lakdawala said, nearly one third of the study participants experienced sudden cardiac death, hemodynamically unstable VA, or an ICD procedure during the 4.2-year follow-up period. In addition, 15% developed advanced heart failure, defined as the implantation of a left ventricular assist device, heart transplant, or nonsudden cardiac death. These outcomes occurred despite many patients having a baseline left ventricular ejection fraction (EF) in the normal range (mean EF was 56%, well above guideline-recommended thresholds of 35%-45% for ICD placement, the researchers reported). Looking deeper into the genes, Lakdawala and his colleagues found participants who had truncating LMNA variants — an abbreviated version of the protein — had worse arrhythmic outcomes, regardless of the position of this genetic mutation on the DNA sequence. On the other hand, those who exhibited missense variants of the LMNA gene — an altered amino acid on the DNA sequence — had a lower risk for harmful arrhythmias and better overall outcomes. Taken together, the location and nature of the gene variants could lead to specific predictions of cardiac risk, according to the researchers. A man with an EF of 50% and a truncating LMNA gene variant, for example, would have a 12% risk for VA within 5 years, but a 7.2% risk if a missense variant were present. For a woman with EF 50%, this risk would be 7.5% for a truncating variant vs 4.5% for a missense variant, if no other risk factors were present. Why Genetic Testing Is Key In an editorial accompanying the journal article, Sharlene M. Day, MD, a cardiomyopathy specialist and presidential professor at the Perelman School of Medicine at the University of Pennsylvania, in Philadelphia, wrote 'the data from this study can also inform risk stratification even in healthy populations with incidental or secondary findings.' Integrating genetic findings into cardiomyopathy management should be 'a priority for all practicing cardiologists,' she wrote. 'The knowledge gap appears to be narrowing with respect to the importance of genetic testing in patients with cardiomyopathies,' Day told Medscape Medical News . 'But there's still opportunity to improve recommendations and referrals by cardiologists for genetic counseling and testing.' Testing typically consists of a broad panel identifying multiple gene variants, including LMNA , she said. If a gene variant is found in an individual patient, cascade testing of family members for that variant is often recommended. 'The current research study nicely highlights the impact of identifying not only the specific gene involved but the type of variation within that gene in terms of risk stratifying patients for adverse outcomes,' she said. Impact on Future Cardiology Guidelines Future clinical practice guidelines should emphasize the value of a genetic diagnosis for risk stratification in patients with dilated cardiomyopathy, especially for predicting sudden death and heart failure, Lakdawala said. The most recent guidelines on heart failure from the American College of Cardiology and the American Heart Association list a class 2A recommendation for placement of an ICD in patients with high-risk genes for dilated cardiomyopathy and an EF of 45% or lower, adding that primary preventive ICD may be considered for those with higher EF. The 2023 European Cardiomyopathy Guideline recommends placement of ICDs in patients with LMNA variants and an EF above 35% (class 2A if risk factors are present and class 2B if no risk factors are present). 'For updated guidelines, I think the most immediate impact would be to refine the LMNA risk score for ventricular arrhythmias to include the type and location of the LMNA variant,' Day told Medscape Medical News . 'Genetic testing has clinical ramifications that will help cardiologists take better care of their patients,' Lakdawala added. 'The take-home message is that they should order these tests!' Lakdawala reported receiving personal fees from Alexion, Bayer, Bristol Myers Squibb, Cytokinetics, Lexeo Therapeutics, Nuevocor, Pfizer, and Tenaya Therapeutics and grants from Bristol Myers Squibb and Pfizer. Day reported serving as chair of the steering committee for Lexicon Pharmaceuticals, on the data monitoring committee for Cytokinetics, and receiving grants from Bristol Myers Squibb.
Reuters
6 days ago
- Business
- Reuters
US judge won't block 23andMe bankruptcy sale to co-founder
July 10 (Reuters) - A federal judge on Thursday declined to block the bankruptcy sale of genetic testing company 23andMe to its co-founder Anne Wojcicki pending the outcome of a legal challenge by California. U.S. District Judge Matthew Schelp in St. Louis, Missouri, during a hearing said he would not pause the $305 million sale while he reviews the state's bid for a declaration that 23andMe cannot sell California customers' genetic data without their consent. A bankruptcy judge rejected those claims on Monday, and California had appealed that ruling to Schelp, who on Tuesday had briefly paused the sale ahead of Thursday's hearing. 23andMe, which filed for bankruptcy in March, is selling its assets to TTAM Research, a new nonprofit founded by Wojcicki. Schelp during the hearing said it was reasonable for U.S. Bankruptcy Judge Brian Walsh to conclude that California customers would not be harmed because they can opt to delete their accounts and genetic information. 'A stay pending appeal threatens to derail the TTAM sale altogether, and creditors and shareholders would likely suffer,' the judge said. Schelp extended the temporary stay until 11:59 p.m. on Friday to give California time to seek a stay from the St. Louis-based 8th U.S. Circuit Court of Appeals. 23andMe, TTAM and the office of California Attorney General Rob Bonta did not immediately respond to requests for comment. California argues the sale violates the state's Genetic Information Privacy Act, which prohibits the transfer and disclosure of genetic data or biological samples to third parties without express permission for each transfer. The state had sought to prevent California customers' data from being transferred, a step that 23andMe said would effectively kill the sale. California consumers represent about 1.8 million of the approximately 10 million genetic profiles in 23andMe's inventory, according to court filings. Walsh, the bankruptcy judge, on Monday overruled California's objections. Other states had also made similar objections to the sale. On Thursday, Bernard Eskandari of the California Attorney General's office told Schelp that the state would have investigated and brought an enforcement action against a company that sold genetic information without consent outside of bankruptcy. And 23andMe customers cannot now be stripped of those protections, he said. 'Bankruptcy is not a hall pass to evade state law,' he said. But Jeff Recher, a lawyer for the company, countered that California's genetic privacy law only regulates the transfer of data and not the sale of equity. 'This is not a transfer of genetic information, it's a sale of an ownership interest," he said. Schelp at the end of the hearing agreed the state law does not apply to sales of ownership and said that California likely lacked standing to challenge the sale. TTAM has said it would continue to protect customers' genetic data and maintain 23andMe's privacy policies, including customers' right to delete their data. Wojcicki was 23andMe's CEO before its bankruptcy filing, and her new nonprofit's name is an acronym formed from the first letters of the words 'twenty-three and me.' TTAM won a bankruptcy auction for 23andMe's assets in June, outbidding a $265 million offer from Regeneron Pharmaceuticals (REGN.O). 23andMe filed for bankruptcy after a drop-off in consumer demand and a 2023 data breach that exposed millions of customers' genetic data. The case is California v. 23andMe Holding Co., U.S. District Court for the Eastern District of Missouri, No. 25-cv-00999. For California: Bernard Eskandari and Daniel Nadal of the Office of the Attorney General of California For 23andMe: Jeff Recher, Chris Hopkins and Paul Basta of Paul, Weiss, Rifkind, Wharton & Garrison For TTAM: Joe Larkin of Skadden Arps Slate Meagher & Flom Read more: Judge briefly pauses 23andMe bankruptcy sale amid California's appeal California fails to stop 23andMe founder from re-acquiring company 23andMe's founder Anne Wojcicki wins bid for bankrupt DNA testing firm DNA testing firm 23andMe files for bankruptcy as demand dries up
New York Times
18-06-2025
- General
- New York Times
Was I Wrong to Tell My Dead Friend's Son That His Father Sold Sperm to a Sperm Bank?
A good friend died 20 years ago, leaving two sons (then 12 and 14). When my friend was in medical school, before he married, he earned money occasionally by selling sperm to a sperm bank. It wasn't a big deal to him; he told me about it. When his older son was 20, he reached out to some of his father's friends on Facebook, asking for old photos and anecdotes. I was happy to provide them, but I decided he was too young to hear about the sperm donations. Fast forward to this year: I emailed his son, now 34, after deciding he had a right to know about the donations. I wanted to warn him in case he was contacted by someone using a genetic testing service. But I never heard back from him. I sent two more emails: an apology if I overstepped and another with more photos. Still no response! Was I wrong to tell him? FRIEND I have no doubt that you meant well. But I believe you misjudged when you told your friend's son about his father's sperm bank activity — in response to a 14-year-old request for photos and cute stories. You don't mention any relationship with these sons. So, it was probably a stretch to decide that you were the right person to warn them about potential siblings — which is entirely speculative, of course. Knowing a fact doesn't oblige us to tell it. You also report that your friend shared the story of his donations easily. So, there are probably other people in his sons' lives who knew and were better suited to decide whether to share this information. (I don't want to imply that your friend did anything wrong, but it can be a sensitive subject.) And his son's silence in response to your three messages suggests that your news was probably unwelcome. Now, we all misfire occasionally. The important thing is not to compound the error by digging in our heels or making excuses. Stop contacting the son. You thought you were being helpful, but you were mistaken. Lesson learned for the next time, right? While They're on a Cruise, We're in the Kennel We are a retired couple and close friends with another retired couple. They travel often, and we have kept their dog in our home many times. Once, we kept the dog for a whole month! They have now announced that they are going on a 100-day cruise, and they expect that we will care for their dog as we have in the past. But we don't want their dog for 100 days. How can we get out of this gracefully? Want all of The Times? Subscribe.
