Ricki Lewis

Seven words someone taking a genetic test doesn’t want to hear:

“You have a variant of uncertain significance.” A VUS.

Instead of a yes or no answer – a gene has a mutation or it doesn’t – a VUS is a “not the usual, but we don’t know if it’s harmful.” A maybe.

But like a typo to just one letter on a page, single DNA base substitutions in a gene’s sequence might not alter the meaning of the encoded protein. This can happen as a change:

• of one three-base codon to another that specifies the same amino acid
• to a similarly-shaped amino acid
• in a part of the protein that’s not essential to it’s function.

Each of us has thousands of variants of uncertain significance, but we don’t know about them unless we take a genetic test. A VUS in a member of a family riddled with certain types of cancer can be stressful, especially if a surgical decision rests on genetic test results.

Misinterpretations can have tragic consequences. Read More 

A report from a clinical trial for a drug to treat the rapid-aging disorder progeria, published in this week’s Journal of the American Medical Association, offers hope for families with the ultra-rare genetic condition.

Old Before Their Time

Children with Hutchinson-Gilford Progeria Syndrome have a distinctive appearance, seemingly hurtling towards old age. After an outwardly normal infancy, weight gain slows, hair thins, joints stiffen, and bones weaken. The gums remain smooth, bereft of erupting teeth. Skin wrinkles as the child’s chubbiness melts away too quickly, and a cherubic toddler begins to resemble a delicate bird.

Beneath the child’s toughening skin, blood vessels stiffen with premature atherosclerosis, fat pockets shrink, and connective tissue hardens. Inside cells, chromosome tips – telomeres – whittle down at a frightening rate, marking time too quickly. But some organs remain healthy, and intellect is spared. The end comes, typically during adolescence, usually from heart failure. Read More 

Imagine a fetus gulping in amniotic fluid and drinking a drug that restores the ability to form teeth, sweat glands and hair that a mutation would otherwise have blocked. Holm Schneider, MD, PhD, at University Hospital Erlangen in Germany and his team have done just that, reporting this week in The New England Journal of Medicine on three toddlers who have avoided symptoms of X-linked hypohidrotic ectodermal dysplasia (XLHED), which they inherited and that affects their older brothers. Read More 

Sailing from New York City to London a century ago took days; today the trip takes hours by air. Similarly, the “diagnostic odyssey” to identify rare diseases has collapsed from years to months, sometimes even less, through the use of exome sequencing and analysis.

A tale of a teen and a tyke with the extremely rare Wiedemann-Steiner syndrome (WSS) argues for the value of earlier exome sequencing in the search for a diagnosis. Read More 

Posts are appearing on my Facebook feed warning against the dangers of eating tilapia. So I decided to do a little research.

My dad was a seafood wholesaler at the Fulton Fish market, and as a kid I’d encountered all manner of fish, at the dinner table and from working one summer at his stall. I knew about porgies, red snapper, flounder, and crabs galore, and that gefilte fish was a mixture of carp, whitefish, and pike. My dad even dealt in turtles and he’d send the occasional mystery species uptown to the American Museum of Natural History for identification.

But I was flummoxed when great bags of shrink-wrapped tilapia fillets began appearing in the supermarket a few years ago.

What the heck is tilapia? Read More 

Is a film based on a video game with fleeting mentions of a biotech buzzword compelling sci-fi? No. But I liked Rampage anyway.

The use of CRISPR to edit genes is perhaps the only novel plot point in this latest monster movie. An evil head of a biotech company subverts a scientist’s work to fashion a bioweapon that revs up the growth hormone gene, and more, in three unfortunate animals. Cue Godzilla, King Kong, and the beast in Lake Placid. Read More 

“DCIS isn’t really cancer. You have nothing to worry about,” said my oncologist confidently.

“Then why am I having a mastectomy in four days?” I blurted.

“DCIS doesn’t spread. So it isn’t cancer.”

“But the “c” stands for carcinoma, a cancer of epithelial tissue. How is that not cancer?” I asked.

“DCIS. Can’t. Spread.”

Case closed. But I knew what he meant. Ductal carcinoma in situ isn’t cancer, some say, because “in situ” means “in place,” and invading healthy tissue is one of the nine characteristics of cancer I’ve listed for years in my textbooks. Eight out of nine was enough to convince me that Hannibal had to go.

Why name my DCIS? Read More 

Having parents who are first cousins doubles the risk of inheriting a single-gene condition, from 2.5 percent to about 5 percent. But it’s harder to quantify risk for psychiatric illnesses because they typically arise from interactions among genes and environmental factors. But now a study from Northern Ireland published in JAMA Psychiatry shows that offspring of cousin-cousin parents are at higher risk for common mood disorders.

The study found that children from these unions face a three-fold increase in the likelihood of taking antidepressants and a two-fold increase in taking antipsychotics. For purposes of the study, taking an antidepressant or antianxiety drug was a stand-in for having a mood disorder and taking an antipsychotic represented conditions with a psychotic component, such as schizophrenia. Read More 

In the world of genome sequencing, donkeys haven’t received nearly as much attention as horses. But now a report on a new-and-improved genome sequence of Willy, a donkey (Equus asinus) jack born at the Copenhagen Zoo in 1997, appears in the new issue of Science Advances, from Gabriel Renaud, of the Centre for GeoGenetics, Natural History Museum of Denmark. (A female is a jenny or jennet.) The new view provides clues to how donkeys may have branched from horses along the tree of evolution. Read More 

"One pill makes you larger, and one pill makes you small," sang Grace Slick in Jefferson Airplane’s classic White Rabbit, conjuring images of Alice in Wonderland in Lewis Carroll’s 1865 novel. But Alice also nibbled a mushroom to grow taller or smaller, following the advice of a hookah-smoking caterpillar perched atop the fungus.

Alice might have munched one of the 200 species of mushroom that produce psilocybin, a hallucinogen. A recent article in Evolution Letters, from Jason Slot, an assistant professor of fungal evolutionary genomics at The Ohio State University and co-workers, reports the sequencing of the genomes of three species of psychedelic mushrooms: Psilocybe cyanescens, Gymnopilus dilepis, and Panaeolus cyanescens. Read More