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Novel phenotype of syndromic premature ovarian insufficiency associated with TP63 molecular defect
Author(s) -
Mathorne Stine W.,
Ravn Pernille,
Hansen Dorte,
BeckNielsen Signe S.,
Gjørup Hans,
Sørensen Kristina P.,
Fagerberg Christina R.
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13725
Subject(s) - hypoplasia , ectrodactyly , premature ovarian insufficiency , ectodermal dysplasia , phenotype , exome sequencing , dysplasia , endocrinology , medicine , premature ovarian failure , biology , genetics , gene
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.