Novel phenotype of syndromic premature ovarian insufficiency associated with TP63 molecular defect

There is growing evidence that TP63 is associated with isolated as well as syndromic premature ovarian insufficiency (POI). We report two adolescent sisters diagnosed with undetectable ovaries, uterine hypoplasia, and mammary gland hypoplasia. A novel paternally inherited nonsense variant in TP63 [NM_003722.4 c.1927C > T,p.(Arg643*)] in exon 14 was identified by exome sequencing. One of the syndromes linked to TP63 is limb mammary syndrome (LMS), an autosomal dominant inherited disorder characterized by ectrodactyly, hypoplasia of mammary-gland and nipple, lacrimal duct stenosis, nail dysplasia, dental anomalies, cleft palate and/or cleft lip and absence of skin and hair defects. The TP63 variant segregated with symptoms of LMS in the family, however, no affected individual had limb defects. The phenotype reported here represents a novel syndromic phenotype associated with TP63. Reported cases with TP63 associated POI are reviewed.