As a result, we identified a compound alteration with two heterozygous variants within the LHCGR gene, which we believe to have contributed to the patient's condition.
To better understand the missense variant, the WT and variant amino acid at codon 11 7 were modeled into the three-dimensional structure of the LHCGR protein (9) (Figure 2).
By performing WES, we identified a compound heterozygous variant in the patient, with a novel missense variant (c.349G>A, p.Gly117Arg) and a novel nonsense variant (c.878C>A, p.Ser293 *) in her LHCGR gene that contributed to the patient's condition.
To date, a total of 77 variants have been identified in the LHCGR gene (Human Gene Mutation Database: http://www.hgmd.cf.ac.uk/), including 49 missenses, 11 nonsenses, five gross deletions, four small insertions, four small deletions, three splicing variants and one gross insertion.
In our case, the nonsense variant (p.Ser293 *) is a loss of function mutation, and our analysis shows that the missense variant (p.Gly117Arg) is mostly likely also a loss of function mutation, which lead to the inactivation of LHCGR. However, the functional analysis is lacking and this should be performed in a future study.
We report a 46, XY, DSD Chinese Uyghur patient with type 1 LCH with novel heterozygous compound variants in the LHCGR gene.
A new variant in signal peptide of the human luteinizing hormone receptor (LHCGR) affects receptor biogenesis causing leydig cell hypoplasia.
Novel compound heterozygous variants in the LHCGR gene identified in a subject with Leydig cell hypoplasia type 1.
Novel homozygous nonsense mutations in the luteinizing hormone receptor (LHCGR) gene associated with 46,XY primary amenorrhea.
Insights into the coexistence of two mutations in the same LHCGR gene locus causing severe Leydig cell hypoplasia.