Research Papers: Pathology:
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
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Santasree Banerjee1,*, Huishuang Chen1,*, Hui Huang1,*, Jing Wu1, Zhiyun Yang2, Weiping Deng3, Dongna Chen1, Jianlian Deng1, Yan Su1, Yang Li1, Chao Wu6, Ye Wang4, Hao Zeng4, Yiming Wang5,1 and Xunhua Li6
1 BGI-Shenzhen, Shenzhen, China
2 Department of Medical Imaging, 1st affiliated hospital, Sun Yat-sen University, Guangzhou, PR China
3 Department of Dermatology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, PR China
4 Department of Medical Genetics, Center for Genome Research, Sun Yat-sen University, Guangzhou, PR China
5 Xinhua College, Sun Yat-sen university, Guangzhou, PR China
6 Department of Neurology, 1st affiliated hospital, Sun Yat-sen University, Guangzhou, PR China
* These authors have contributed equally to this work
Xunhua Li, email:
Yiming Wang, email:
Keywords: microcephaly 2, WDR62 mutation, compound heterozygosity, novel mutations, exome sequencing, Pathology Section
Received: June 25, 2016 Accepted: November 01, 2016 Published: November 10, 2016
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.
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