Journal article

Publication year: 2005

Pages: 255-259

Journal: European journal of endocrinology

Volume number: 152

Issue number: 2

ISSN: 0804-4643

eISSN: 1479-683X

Open access status: Bronze

DOI Link: https://doi.org/10.1530/eje.1.01852

Publisher: Oxford University Press

Abstract: 
Leydig cell hypoplasia (LCH) is a rare autosomal recessive condition that interferes with normal development of male external genitalia in 46,XY individuals and is caused by inactivating mutations of the LH receptor gene. The clinical and biochemical diagnostic parameters of LCH are not always specific and may therefore show significant overlap with other causes of insufficient testicular steroid biosynthesis. We have studied a 46,XY newborn with completely female external genitalia and palpable testes. Due to an increased basal serum ratio of androstenedione/testosterone, 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD 3) deficiency was initially suspected. DNA analysis of the corresponding HSD 17B3 gene, however, showed no abnormalities in the entire coding region. In contrast, direct sequencing of the LH receptor gene revealed a novel homozygous single nucleotide insertion in exon 11 (codon A589fs) producing a frame shift in the open reading frame predicting for premature termination of translation 17 amino acids downstream. From the genetic perspective, this mutation represents the first frame shift mutation in the LH receptor gene ever reported to date. From the clinical standpoint, LCH should always be considered in the differential diagnosis as steroid profiles may not be informative. Therefore, molecular genetic analysis should be warranted for androgen biosynthesis defects in all cases.

Harvard Citation style: Richter-Unruh, A., Korsch, E., Hiort, O., Holterhus, P., Themmen, A. and Wudy, S. (2005) Novel insertion frameshift mutation of the LH receptor gene: problematic clinical distinction of Leydig cell hypoplasia from enzyme defects primarily affecting testosterone biosynthesis, European journal of endocrinology, 152(2), pp. 255-259. https://doi.org/10.1530/eje.1.01852

APA Citation style: Richter-Unruh, A., Korsch, E., Hiort, O., Holterhus, P., Themmen, A., & Wudy, S. (2005). Novel insertion frameshift mutation of the LH receptor gene: problematic clinical distinction of Leydig cell hypoplasia from enzyme defects primarily affecting testosterone biosynthesis. European journal of endocrinology. 152(2), 255-259. https://doi.org/10.1530/eje.1.01852