Ursula Kaiser, MD______

A research team led by Ursula Kaiser, MD, chief of the BWH Division of Endocrinology, Diabetes and Hypertension, in a multi-institutional collaboration with Boston Children’s Hospital, the Broad Institute, and the University of Sao Paulo, Brazil, identified that a genetic mutation leads to a type of premature puberty, known as central precocious puberty. Central precocious puberty is defined by the development of secondary sexual characteristics before age eight years in girls and nine years in boys.

The researchers performed whole exome sequencing analysis of forty individuals from fifteen families with central precocious puberty. In five of the fifteen families, the researchers identified four mutations in the MKRN3 gene, which is responsible for coding a protein called makorin ring finger protein 3. The genetic mutations resulted in truncated MKRN3 proteins and disruption of MKRN3 protein function.

They also found that affected individuals inherited the mutations from their fathers. Moreover, the MKRN3 gene is located on the same chromosome as genes for Prader-Willi syndrome, a rare condition that results in short stature, incomplete sexual development, cognitive disabilities, insatiable appetite and severe obesity, among other abnormalities; although, despite being on the same chromosome, MKRN3 is not thought to contribute to the clinical features of Prader-Willi syndrome.

“These findings will open the door for a new understanding of what controls the timing of puberty,” said Kaiser. “It also will allow doctors to diagnose the cause of precocious puberty in a subset of patients, or to identify patients at risk for developing precocious puberty, especially if others in their family are affected. By better understanding the role of this gene in the timing of puberty, we may be able to gain insights into how other factors, such as environmental factors, may influence pubertal timing.”

The study was published online June 5, 2013 in The New England Journal of Medicine.