Growing up can be awkward, especially for kids with central precocious puberty (CPP), who start developing sexual features when they are just 8 to 9 years old. An international collaboration of doctors from Boston and Brazil has linked a subset of CPP cases to a mutation in dads. The finding, published today in the New England Journal of Medicine, could help explain why some kids mature faster than others.
"These findings will open the door for a new understanding of what controls the timing of puberty," said co-senior author Dr. Ursula Kaiser, chief of the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women's Hospital in Boston. She conducted the study with help from researchers at Boston Children's Hospital, the Broad Institute, and the University of Sao Paulo, Brazil.
Early puberty affects as many as one in 5,000 kids and is connected to a higher risk for future diseases like breast cancer, obesity, and cardiovascular disease.
Central precocious puberty is an extreme version of early puberty that typically strikes girls at a younger age than boys. The youngest case on record is a girl from Peru named Lina Medina, who gave birth when she was five years old.
While the underlying cause is unknown, all CPP cases are marked by a chemical imbalance of gonadotropin-releasing hormone in the brain's hypothalamus. Levels of this hormone are low throughout childhood, but begin to rise around the age of 11 and triggers the maturation of reproductive organs and functions.
While some instances of CPP are linked to tumors or infections in the hypothalamus, nearly one in four cases are thought to be inherited.
The researchers recruited 15 families with a history of CPP and analyzed their genes for possible mutations.
Genome sequencing revealed five of the 15 families carried a mutation in the MKRN3 gene. The inheritance pattern suggested fathers were responsible for passing the mutation onto affected CPP individuals, which was further supported by a quirk in the MKRN3 gene.
A person normally carries two copies of every gene. One is inherited from your mom, while the other comes from your pop. Sometimes one parent donates a copy of the gene that is turned off, which is known as gene imprinting. MKRN3 is maternally imprinted, which means that only the copy from the father is turned on.
The researchers also found that the brain levels of MKRN3 are high in young mice, but decline right before they enter puberty. Further research is needed to resolve MKRN3's role in human puberty.
"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," continued Kaiser.
The results will also be presented at The Endocrine Society's 95th Annual Meeting & Expo in San Francisco on June 17, 2013.
Source: Abreu AP, Dauber A, Macedo DB, et al. Central Precocious Puberty Caused by Mutations in the Imprinted Gene MKRN3. NEJM. 2013.