Novel variants in LSS related hypotrichosis simplex 14

Hypotrichosis simplex (HS) is a rare form of hereditary alopecia caused by a variety of gene variants, with onset in childhood. Few studies regarding LSS-related HS(HS 14) have been reported and genotype-phenotype correlations in the LSS gene are still not completely clear.

In this study, we tried to make a definite diagnosis in two Chinese pediatric patients clinically suspected of congenital hypotrichosis. Peripheral blood samples of these two patients and their parents were collected and whole-exome sequencing (WES) was performed to elucidate the genetic cause. WES revealed four different compound heterozygous variants in LSS in two probands that confirmed a diagnosis HS 14, including two novel variants. AlphaFold two was performed to predict three-dimensional structures, and the PROVEAN analysis software was utilized to assess the functional changes of novel missense variant.

Two previously reported variants,c.1054G>A; p.(Gly352Arg) and c.1303C>T; p.(Arg435Cys) were observed and two novel heterozygous variants,c.1594G>C; p.(Glu532Gln) and c.1010C>T; p.(Pro337Leu) were found in these 2 HS patients.

In this study, we successfully identified variants in LSS in two probands that confirmed a diagnosis of HS, including two novel variants. These findings expanded the variantal spectrum of LSS-related HS 14. Moreover, teeth dysplasia could be an associated phenotype in patient with HS 14.