Whole exome sequencing detects a heterozygous missense mutation in PGBD3 
Whole exome sequencing was performed in the three known affected casesⅡ3, Ⅱ11 and Ⅲ5; one genetically obligate male carrier (Ⅱ5) should a mutation be segregating in autosomal dominant fashion; and one normal family member Ⅱ9. More than 20,000 single-nucleotide variants (SNVs) were identified in each subject. After being “blasted” with public databases, verified by Sanger sequencing, and sequencing the remaining family members (Ⅱ1, Ⅱ2, Ⅱ6, Ⅱ7, Ⅱ8, Ⅱ10, Ⅲ1, Ⅲ2, Ⅲ3, Ⅲ6, Ⅲ7, Ⅲ8, Ⅲ9, Ⅲ10, Ⅲ11, Ⅲ12, Ⅲ13), only the heterozygous variant (ENST00000515869: c.2237G>A, p.G746D) in PiggyBac transposable element derived 3 (PGBD3) was exclusively carried by those affected individuals (Ⅱ3, Ⅱ11, Ⅲ2 and Ⅲ5), and the obligate carrier (Ⅱ5), and absent in normal family members. Ⅲ2 and Ⅲ5 inherited the variant from their fathersⅡ2 and Ⅱ5, respectively, supporting autosomal dominant inheritance (Table 1 and Fig 1).
10.1371/journal.pgen.1005419.t001 Table 1  Clinical features of index family and 2 sporadic POF patients with mutations in CSB-PGBD3.     *1–2 mg daily dose of oral estradiol valerate tablet for 21 days plus oral micronized progesterone (200 mg/d) for 12 days each month.

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