June 10, 2013
1 min read

Genetic mutation responsible for precocious puberty identified

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Mutations in a paternally inherited gene may cause precocious puberty, according to data published in the New England Journal of Medicine.

“The timing of puberty is associated with risks of subsequent disease; earlier age of menarche in girls is associated with increased risks of breast cancer, endometrial cancer, obesity, type 2 diabetes, and cardiovascular disease,” researchers wrote.

To understand and identify genetic causes of central precocious puberty, Ana Paula Abreu, MD, PhD, from the division of endocrinology, diabetes and hypertension at Brigham and Women’s Hospital and Harvard Medical School, and colleagues conducted a whole-exome sequencing of 40 members from 15 families with known central precocious puberty.

The researchers also evaluated levels of messenger RNA (mRNA) in the hypothalami of mice at various ages using quantitative real-time polymerase-chain reaction assays.

Abreu and colleagues identified four novel heterozygous mutations in MKRN3 in five of the 15 families, according to data. The mutations impacted both sexes.

Furthermore, the researchers found that MKRN3 is a paternally-expressed, imprinted gene located in the Prader-Willi syndrome chromosome region.

“The deletion of chromosome 15q11-q13, which encompasses MKRN3, contributes to the Prader-Willi syndrome, but it is not yet known which specific genes in this region are related to the syndrome,” the researchers wrote.

After analyzing the mice hypothalami, the researchers noted high levels of Mkrn3 mRNA in the arcuate nucleus of prepubertal mice, which decreased immediately before puberty and remained low thereafter.

They conclude that MKRN3 deficiency causes an inhibitory effect on the secretion of GnRH, or central precocious puberty.

Disclosure: See the study for a full list of disclosures.