As was stated, homozygous pearl is lethal in utero. There has not been any indication that this is necessarily a problem though, just means you might have smaller than normal litters.

There is another gene that is lethal homozygous. I want to say it is true roan, but I need to look up the sources again. Part of the confusion is there are several different varieties that are called "roan". Like pearl, it is lethal in utero.

Also as was stated, blue rats, whether American/British blue or Russian blue (two different genes) are no healthier or unhealthier than any other variety. It depends on the strain/bloodline you are using and what is present in that line. While I was breeding rats, I had a true breeding line of Russian blue, and had no issues with them. In the past American/British blue were thought to have bleeding issues (where the blood wouldn't clot even from small wounds), but that has proven to be a bloodline trait, and not a color trait. Other lines of blue have had no issues.

Rex bred to rex does have a chance to produce double rex/patchwork hairless, but quality will vary. Some will be nearly hairless, others will be patchy, still others may simply look like short-coated rex. The statistics are 25%, but of course reality can vary from the statistics, so a litter of rex x rex could have a couple double rex, lots of double rex, or no double rex.

Another issue to be aware of is megacolon. It is genetic, linked to a spotting gene commonly (and inaccurately) called "high white". If you know anything about horse genetics, megacolon in rats resembles overo lethal white syndrome (OLWS) in horses. In horses the foal is born completely white and dies within 72 hours (if not euthanised before then) because their colon is unable to function properly. In rats, megacolon also affects the function of the colon, but usually does not become apparent until around 3 weeks of age when the young rats start to eat solid foods. Before then, they may show signs of failure to thrive. When megacolon starts to affect them, their stomachs may become bloated and they may be unable to pass feces normally. Eventually they do die, although some people have successfully kept these rats alive on special diets. These rats are often called “high white”, but that is a misnomer. Rats affected with megacolon may be nearly completely white, have only a little white, or may have almost no white or even be solid (self) colored, and these rats may come from parents who have very little or a lot of white. The problem is not the coloration necessarily, but the genes behind it. The current scientific thought is there are actually two genes responsible. One is thought to be a dominant white spotting gene (note: this is NOT the same gene responsible for more common recessive white spotting, such as hooded, Berkshire, or even variegated or capped), the other is thought to be the gene directly responsible for megacolon when combined with the dominant white spotting gene.