Novel mutation in FTHL17 gene in pedigree with 46,XY pure gonadal dysgenesis

We describe the first 46,XY PGD pedigree that is likely mediated by gene mutations of FTHL17, which is located in Xp21.2 and probably associated with the testis-determining pathway and tumorigenesis.

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Volume 111, Issue 6, Pages 1226–1235.e1


Ruiyi Tang, M.Sc., Xiao Liu, Ph.D., Lingya Pan, M.D., Rong Chen, M.D.



To identify the genetic cause of a pedigree with four patients with 46,XY pure gonadal dysgenesis (PGD).


Genetic mutation study.


Academic medical center.


Four first cousins, from three households of a Chinese pedigree, affected by 46,XY PGD.



Main Outcome Measure(s)

The patients were studied from clinical and genetic perspectives. Whole-genome sequencing was conducted in family members.


Four first cousins in the third generation were affected by 46,XY PGD. A specific familial characteristic was the prevalence of as high as 100% of gonadal tumors in patients. Whole-genome sequencing identified a new ferritin heavy chain–like 17 (FTHL17) mutation, c.GA442_443TT (p.E148L), which has the potential to interfere with protein function and cause 46,XY PGD. Moreover, the location (Xp21.2) of the FTHL17 gene proves that the family is X-linked recessive. In vitro functional study revealed that the perturbation of FTHL17 caused the decrease of protein expression and cell proliferation.


We describe the first 46,XY PGD pedigree that may be attributed to mutations of the FTHL17 gene. We speculated that the FTHL17 gene is involved in the testis-determining pathway and tumorigenesis.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.