Novel mutations c.28G>T (p.Ala10Ser) and c.189G>T (p.Glu63Asp) in WDR62 associated with early onset acanthosis and hyperkeratosis in a patient with autosomal recessive microcephaly type 2

Oncotarget. 2016 Nov 29;7(48):78363-78371. doi: 10.18632/oncotarget.13279.


Microcephaly (MCPH) is a developmental disorder characterized by reduced brain size and intellectual disability. A proportion of microcephaly is caused by defects in a single gene. Microcephaly 2 (MCPH2) is one of the most frequent subtypes of MCPH.WD repeat-containing protein 62 gene (WDR62) is the most frequently mutated gene in MCPH2 patients. Phenotypes involving dermatological changes in MCPH2 have not been reported. We have identified and investigated a 5-year-old Chinese girl with markedly reduced brain size (86% of normal size), intellectual disability and psychomotor developmental delay. The patient also exhibited spattered blisters and reduced hair density on her head, anisochromasia with reticular hyperpigmentation and hypopigmentation on the trunk, which she has had since the age of 4 and had been found by her parents. Histological examination of a skin biopsy revealed acanthosis, hyperkeratosis and necrotic keratinocytes. Whole exome and Sanger sequencing identified two novel missense mutations, c.28G>T and c.189G>T, in the WDR62 gene. Both the mutations non-synonymously affect evolutionarily conserved amino acids and are predicted to be disease causing. We report the first case of MCPH2 that also presented with marked dermatological changes. Our findings expand the mutational and phenotypical spectra of MCPH2 and are valuable in the mutation-based pre- and post-natal screening and genetic diagnosis for MCPH2.

Keywords: Pathology Section; WDR62 mutation; compound heterozygosity; exome sequencing; microcephaly 2; novel mutations.

Publication types

  • Case Reports

MeSH terms

  • Acanthosis Nigricans / diagnosis
  • Acanthosis Nigricans / genetics*
  • Biopsy
  • Cell Cycle Proteins
  • Child Behavior
  • Child Development
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics
  • Intellectual Disability / psychology
  • Magnetic Resonance Imaging
  • Microcephaly / diagnosis
  • Microcephaly / genetics*
  • Microcephaly / physiopathology
  • Microcephaly / psychology
  • Mutation, Missense*
  • Nerve Tissue Proteins / genetics*
  • Phenotype
  • Psychomotor Disorders / diagnosis
  • Psychomotor Disorders / genetics
  • Psychomotor Disorders / psychology
  • Psychomotor Performance
  • Skin / pathology*
  • Skin Pigmentation / genetics*


  • Cell Cycle Proteins
  • Nerve Tissue Proteins
  • WDR62 protein, human

Supplementary concepts

  • Microcephaly, Primary Autosomal Recessive, 2