Whole-exome sequencing performed in 40 members of 15 families with central precocious puberty identified 304,930 variants. Rigorous criteria were used to filter the variants and identify the mutations likely to be causative of the phenotype for central precocious puberty. We first analyzed exome-sequence data from a total of 15 members of the 3 largest families with pedigrees that were consistent with a dominant mode of inheritance (i.e., those families having affected members in multiple generations). Among the persons who underwent exome sequencing, we identified heterozygous nonsynonymous variants that were present in affected family members and absent in unaffected family members. Given the dominant inheritance pattern and rarity of presentation of familial precocious puberty, we excluded all variants with a minor allele frequency of more than 0.01% in either the 1000 Genomes database25 or the exome variant server.26 In addition, we excluded all putative variants that were also present in 50 of the 1000 Genomes control samples included in the variant calling process. In applying these criteria, we identified candidate genes within each family (4 in Family A, 65 in Family
