BG08: A new variant in HOXC13 associated with a severe phenotype of pure hair and nail ectodermal dysplasia

Posters

Geraldine Quinn,¹ Edel O’Toole,^2,3 Catherine Dennis⁴ and Kapila Batta¹

¹Watford General Hospital, Watford, UK; ²Queen Mary University, London, UK; ³Royal London Hospital, London, UK; and ⁴North West Thames Regional Genetics Service, London, UK

Pure hair and nail ectodermal dysplasia (PHNED) is a congenital disorder characterized by the presence of sparse to absent hair on the scalp and body and dystrophic nails without abnormalities of other ectodermal and nonectodermal structures. Both autosomal dominant and recessive forms have been described. Pathogenic mutations in KRT85 and HOXC13 have been described in autosomal recessive forms. Here we report a new autosomal recessive variant of HOXC13 in a Sri Lankan child with nonconsanguineous parents associated with a severe form of PHNED. A 2-month-old Sri Lankan child with unrelated parents presented with complete absence of body hair since birth. All 20 nails were dystrophic, small and poorly developed. She has been followed-up until the age of 15 years. She had some follicular openings on her scalp, but the clinical appearance has otherwise remained unchanged. Her teeth and sweating were normal. She had normal development and no other abnormal findings. No other family members were similarly affected. Genetic analysis revealed no mutations of KRT85. Whole-genome sequence analysis showed homozygosity for HOXC13 c.931C> T variant. Both parents are heterozygous for this variant, which provides further potential evidence for its pathogenicity. HOXC13 is an important regulator of hair and nail growth and development. It encodes a 330-amino acid protein that acts as a transcription regulator of keratin and keratin-associated protein genes. Only six previous mutations in HOXC13 resulting in PHNED have been previously described (Mehmood S, Raza SI, Van Bokhoven H et al. Autosomal recessive transmission of a rare HOXC13 variant causes pure hair and nail ectodermal dysplasia. Clin Exp Dermatol 2017; 42: 585–9; Li X, Orseth ML, Smith JM et al. A novel homozygous mutation in HOXC13 lead to pure hair nail ectodermal dysplasia. Pediatr Dermatol 2017; 34: 172–5). This new variant, resulting in a severe phenotype, is the first in a nonconsanguineous family and expands the mutation spectrum of HOXC13 in PHNED. Further research is being undertaken into the pathogenicity of this new variant.