Hereditary spastic paraplegia masqueraded by congenital melanocytic nevus syndrome: Dual pathogenesis of germline non-mosaicism and somatic mosaicism

Yuri Sakaguchi, Tomoko Uehara, Marie Sasaki, Kimino Fujimura, Kazuo Kishi, Kenjiro Kosaki, Toshiki Takenouchi

Research output: Contribution to journalArticle

Abstract

Neurocutaneous disorders are caused by germline and/or somatic mutations and involve the integument and central nervous systems. Congenital melanocytic nevus syndrome is characterized by melanotic skin lesions caused by somatic mutations at codon 61 in NRAS. A large cutaneous lesion raises the risk of central nervous system involvement. We report an 8-year-old girl with a congenital giant pigmented nevus that covered almost her entire back. Despite the absence of any radiological evidence of intracranial melanosis, the patient exhibited progressive limb spasticity with preserved intellectual ability. An extensive genetic analysis identified a specific class of heterozygous germline mutation in SPAST, p.(Arg499His), which is responsible for hereditary spastic paraplegia with infantile onset. In addition, a known heterozygous somatic mutation in NRAS, p.(Gln61Lys) was detected in the cutaneous lesion. This observation recapitulates concomitant mosaicism and non-mosaicism within a single individual and suggests that the possibility of a dual genetic diagnosis should be considered when neurological decline is observed in a patient with a neurocutaneous disorder without any detectable intracranial lesions.

Original languageEnglish
Article number103803
JournalEuropean Journal of Medical Genetics
Volume63
Issue number4
DOIs
Publication statusPublished - 2020 Apr

Keywords

  • Congenital melanocytic nevus syndrome
  • Hereditary spastic paraplegia
  • NRAS
  • Neurocutaneous disorder
  • SPAST

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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