A receptor mutation that essentially blocks estrogen’s action has been identified for the first time in a female, researchers report.

The 18-year-old wasn’t experiencing breast development or menstruation, classic symptoms of too little estrogen, the usual cause of delayed puberty. Subsequent studies revealed instead sky-high levels of the sex hormone in her blood, said Dr. Lawrence C. Layman, Chief of the Section of Reproductive Endocrinology, Infertility and Genetics at the Medical College of Georgia at Georgia Regents University.

“Her body totally ignores estrogen,” Layman said. “Even at levels that are 10 to 15 times normal, it has no effect.” In fact, in laboratory studies, 240 times the normal level was required to get a response out of the receptor.

There are two confirmed estrogen receptors, and genetic testing subsequently determined she had a mutation in estrogen receptor-α, which is essential to reproduction and bone health, researchers report in the New England Journal of Medicine. Estrogen levels in her blood were comparable to those of a mouse whose estrogen receptor-α gene has been deleted.

Interestingly the first mutation in this receptor was reported nearly 20 years earlier in the NEJM in a 28-year old man with knock-knees and signs of insulin resistance. Studies showed his testosterone levels were normal and, although his estrogen and related hormone levels were high, he also had essentially no response to estrogen. The research team, led by Children’s Hospital Medical Center in Cincinnati, found the estrogen receptor defect, concluding that estrogen is important to bone health in men as well as women.

The cellular cause of birth defects like cleft palates, missing teeth and problems with fingers and toes has been a tricky puzzle for scientists.

Now Professor Emily Bates and her biochemistry students at Brigham Young University have placed an important piece of the developmental puzzle. They studied an ion channel that regulates the electrical charge of a cell. In a new study published by the journal Development, they show that blocking this channel disrupts the work of a protein that is supposed to carry marching orders to the nucleus.

Without those instructions, cells don't become what they were supposed to become -- be that part of a palate, a tooth or a finger. Though there are various disorders that lead to birth defects, this newly discovered mechanism may be what some syndromes have in common.

Bates and her graduate student, Giri Dahal, now want to apply the findings toward the prevention of birth defects -- particularly those caused by fetal alcohol syndrome and fetal alcohol spectrum disorder.

Critical insight provided into the disease mechanisms behind multiple sclerosis.

Scientists have identified 29 new genetic variants linked to multiple sclerosis, providing key insights into the biology of a very debilitating neurological disease. Many of the genes implicated in the study are relevant to the immune system, shedding light onto the immunological pathways that underlie the development of multiple sclerosis.

The research, involving an international team of investigators led by the Universities of Cambridge and Oxford and funded by the Wellcome Trust, is published today, 11 August, in the journal Nature. This is the largest MS genetics study ever undertaken and includes contributions from almost 250 researchers as members of the International Multiple Sclerosis Genetics Consortium and the Wellcome Trust Case Control Consortium.