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

• Published in: Clinical genetics 2020-05, Vol.97 (5), p.779-784
• Main Authors: Mathorne, Stine W., Ravn, Pernille, Hansen, Dorte, Beck‐Nielsen, Signe S., Gjørup, Hans, Sørensen, Kristina P., Fagerberg, Christina R.
• Format: Article
• Language: English
• Subjects: Cleft lip/palate; Dysplasia; Ectrodactyly; Genotype & phenotype; Hereditary diseases; Hypoplasia; limb mammary syndrome; Mammary gland; mammary hypoplasia; Ovaries; Phenotypes; premature ovarian insufficiency; Stenosis; TP63; uterine hypoplasia; Uterus
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.13725

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. There is growing evidence that the TP63 gene is associated with premature ovarian insufficiency (POI). We present a novel TP63 associated syndromic phenotype in a family where two sisters were diagnosed with POI. The TP63 variant segregated with features of limb mammary syndrome, except that none of the affected individuals had limb defects.