Two cases of severe congenital hypotrichosis caused by compound heterozygous mutations in the LSS gene

Abstract

It has recently been shown that bi‐allelic mutations in the lanosterol synthase (LSS) gene, which was originally reported as a causative gene for congenital cataracts, underlie a non‐syndromic form of hypotrichosis. Furthermore, it has also been revealed that mutations in the LSS gene can cause syndromic forms of hypotrichosis. To date, however, clear genotype–phenotype correlations have not completely been characterized. In this study, we identified two Japanese patients who had severe congenital hypotrichosis without any other associated findings. Their scalp hairs were extremely short and thin, and were able to be plucked easily. Observation of the plucked hairs showed aberrantly‐miniaturized anagen hair follicles. Genetic analysis demonstrated that both patients carried bi‐allelic mutations in the LSS gene in a compound heterozygote state. Our findings further underscore the crucial roles of the LSS gene in hair follicle development and hair growth in humans.

Four hypotrichosis families with mutations in the gene LSS presenting with and without neurodevelopmental phenotypes

“…Both parents were heterozygous carriers of the mutation (Figure 1a). Recent studies reported this mutation occurring in a compound heterozygous state, together with other mutations, in two further hypotrichosis patients, who presented with and without ID, respectively (Murata et al, 2021;Wada et al, 2020).…”

Novel LSS variants in alopecia and intellectual disability syndrome: New case report and clinical spectrum of LSS‐related rare disease traits

“…13 Several families with the HS phenotype have been described with the variants spread across both domains. [8][9][10][11]14,18 Then the phenotypic spectrum of LSS was expanded to include a third and more severe neuro-ectodermal phenotype, APMR4, with a report of 11 patients from seven unrelated families having alopecia and intellectual disability secondary to LSS biallelic variants. 2 The described LSS variants were distributed across both LSS domains thus providing no clear phenotype-genotype correlation (Figure 1D).…”

“…6 A total of 29 families with all three LSS-related disorders have been reported worldwide amongst which are 10 families with 15 affected individuals with the APMR4 phenotype. 2,5,[7][8][9][10][11][12][13][14][15][16][17][18] We describe an Egyptian patient with biallelic novel variants in LSS and APMR4 to potentially expand the mutational and phenotypic spectrum of the syndrome.…”

“…A total of 29 families with all three LSS ‐related disorders have been reported worldwide amongst which are 10 families with 15 affected individuals with the APMR4 phenotype 2,5,7–18 …”

A novel homozygous mutation in LSS gene possibly causes hypotrichosis simplex in two siblings of a Tibetan family from the western Sichuan province of China

“…Biallelic mutations in LSS were first reported in families with congenital cataracts (Zhao et al, 2015;Romano et al, 2018). More recently, several studies have identified mutations in the lanosterol synthase encoding gene LSS from patients affected by hypotrichosis simplex, suggesting LSS could also be associated with the disease (Li et al, 2019;Cesarato et al, 2021;Murata et al, 2021). Nevertheless, the pathophysiological mechanism of how its mutations cause hypotrichosis simplex remains unclear.…”