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Piebaldism resulting from a novel deletion mutation of KIT gene in a five‐generation Chinese family

Piebaldism is an autosomal dominant genetic disorder of depigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Mutations of the KIT and SNAI2 genes have been reported as ascertained aetiological factors of human piebaldism. We report a rare case of piebaldism in a fivegeneration Chinese family. A 2-month-old female infant presented with skin depigmentation patches and poliosis, which had been present since birth. Her mother reported no deafness or aberrant ocular signs. Four of the child’s relatives had similar physical symptoms (Fig. 1a). On physical examination, the child was seen to have partial white hairs on the forehead, different sizes of depigmented patches distributed symmetrically on the middle part of her legs and left side of the abdomen were observed (Fig. 1b). A primary diagnosis of piebaldism was made. To confirm this diagnosis, whole-exome sequencing of the proband’s family was performed. A heterozygous variant in KIT gene (NM_000222) revealed a deletion mutation (c.1842–1843 AG) in exon 12, which leads to a frameshift at amino acid position 614 (Fig. 1c). Genetic analysis of the proband’s mother and three of the affected relatives showed the same variation, whereas it was not seen in the proband’s father. Human piebaldism was first reported by Giebel and Spritz in 1991. Based on the size of the leucoderma and the presence/absence of the white forelock, piebaldism is classified into three phenotypes: mild, moderate and severe. The mild form presents with only a white forelock or small areas of leucoderma on the forehead, ventral trunk or extremities, whereas the severe form displays a typical white forelock on the frontal scalp and relatively large areas of leucoderma on the chest, abdomen, arms and legs. The moderate phenotype falls between the other two. Overlapping clinical manifestations, mainly focused on the leucoderma, can appear in Waardenburg syndrome, which may involve congenital sensorineural hearing loss, heterochromatic irises, dystopia canthorum and musculoskeletal abnormalities. The clinical phenotype of patchy hypopigmentation, including the pattern, distribution and extent, is similar in patients with heterozygous deletions of the SNAI2 gene and in those with mutations in the KIT gene. The KIT gene encodes the protein KIT (also known as mast cell/stem cell growth factor), which is associated with the proliferation, migration, differentiation and survival of melanocytes, while the SNAI2 protein (also known as SLUG), contributes to encode zinc-finger neural crest transcription factor, which is implicated in the development of human melanocytes. Therefore, deficiency or mutation in both the KIT and SNAI2 genes may work synergistically on the production of the melanocytes or pigmentation, supporting the classic clinical findings of leucoderma and white forelock in human piebaldism. A deletion mutation in the tyrosine kinase domain 1 of the KIT gene has been reported once previously in a patient with a moderate form of piebaldism. No such deletion variant was identified in the SNAI2 gene. Treatment of piebaldism includes split-thickness grafting, epidermal blister grafting, cultured melanocyte grafting or epidermal suspension grafting, punch Correspondence: Dr Li Li, Department of Dermatology and Venereology, West China Hospital, Sichuan University, Guoxue Alley No. 37, Wuhou District, Chengdu, China E-mail: lilihx_scu@scu.edu.cn