Hypotrichosis 14

A number sign (#) is used with this entry because of evidence that hypotrichosis-14 (HYPT14) is caused by homozygous or compound heterozygous mutation in the LSS gene (600909) on chromosome 21q22.

Description

Hypotrichosis-14 is characterized by sparse to absent lanugo-like scalp hair, sparse and brittle eyebrows, and sparse eyelashes and body hair (Romano et al., 2018).

For a discussion of genetic heterogeneity of hypotrichosis, see HYPT1 (605389).

Clinical Features

Romano et al. (2018) reported 3 unrelated families with hypotrichosis simplex. In the first family, 2 Arab sisters presented at birth with sparse lanugo-like scalp hair and short brittle eyelashes, and underwent pronounced scalp hair loss with partial loss of eyebrows and eyelashes in primary school. Examination at ages 16 and 19 years showed sparse scalp hair with paucity of body hair. In an Afghan family, a brother and sister, their father, and a paternal uncle presented with hypotrichosis. All 4 exhibited sparse lanugo-like scalp hair and sparse brittle eyebrows, with normal eyelashes and normal hair on extremities, but sparse pubic hair and absence of axillary hair. In addition, a Swiss brother and sister who were examined in adolescence showed sparse lanugo-like scalp hair, sparse brittle eyebrows, sparse thin eyelashes, sparse hair on extremities, and absence of axillary and pubic hair. Both of the Swiss sibs also displayed intellectual disability, which the authors considered to be coincidental.

Molecular Genetics

In 2 Arab sisters with nonsyndromic hypotrichosis, who were negative for mutation in known autosomal recessive hypotrichosis-associated genes, Romano et al. (2018) performed whole-exome sequencing and identified homozygosity for a missense mutation in the LSS gene (F391S; 600909.0005). Screening the LSS gene in a cohort of patients with hypotrichosis simplex revealed 2 more families with mutations in LSS: an Afghan family in which affected individuals were compound heterozygous for 2 missense mutations (L248P, 600909.0006 and L102V, 600909.0007), and a Swiss brother and sister who were compound heterozygous for a nonsense mutation (W141X; 600909.0008) and a missense mutation (N209Y; 600909.0009). The mutations, which clustered toward the N terminus of LSS, segregated with disease in the families and were either not present or found at very low frequency in heterozygous state in the ExAC and gnomAD databases.

Genotype/Phenotype Correlations

Romano et al. (2018) noted that Zhao et al. (2015) identified homozygous mutations in the C-terminal domain of LSS (G588S, 600909.0001 and W581R, 600909.0002) in patients with congenital cataract (CTRCT44; 616509). In addition, Chen and Liu (2017) reported a Chinese boy with an intermediate phenotype, showing both congenital cataract and hypotrichosis, who was compound heterozygous for missense mutations in the LSS gene: I342S (600909.0003) in the N-terminal domain and W629C (600909.0004) in the C-terminal domain. Romano et al. (2018) suggested a genotype/phenotype correlation, with mutations occurring toward the N terminus giving rise to hair loss, and mutations toward the C terminus being associated with ocular abnormalities.