Familial progressive hyper- and hypopigmentation: a report on a Chinese family and evidence for genetic heterogeneity

Abstract

BackgroundFamilial progressive hyper- and hypopigmentation (FPHH) is a rare genodermatosis that is characterized by diffuse hyper- and hypopigmented spots on the skin and mucous membranes. It is caused by a pathogenic mutation of the KITLG gene.ObjectivesTo investigate the clinical features and mutation of the KITLG gene in a Chinese family with FPHH.MethodsHistopathological and immunohistochemical analysis of lesions from the proband was performed. The KITLG gene was screened for the presence of mutations.ResultsA Chinese family containing 14 individuals with FPHH was described, and the proband was a 5-year-old girl showing diffuse hyper- and hypopigmented lesions on her extremities and trunk. Histopathological and immunohistochemical staining for S100 and HMB45 of skin biopsy specimens from the hyperpigmented areas showed a striking increase in melanin throughout the epidermis, especially in the basal cell layer, and staining of hypopigmented area specimens displayed lower levels of melanin in the epidermis. Mutation analysis of the KITLG gene was performed, but no mutation was found.Study limitationsThe new pathogenic gene was not found.ConclusionA family with FPHH was described. Analysis revealed that its members did not have any mutations of the KITLG gene, which provided evidence for genetic heterogeneity of this genodermatosis.

Pigmentary Changes in a Woman With Oral Lichen Planus

“…The underlying gene is KITLG. 2,5 Lastly, XP is an autosomal recessive disorder characterized by increased sensitivity to UV radiation. An early clinical sign is severe sunburn after short sun exposure during infancy.…”

“…Biopsy specimen taken from hyperpigmented patches show increased melanin in the basal layer, whereas hypopigmented patches show decreased melanin. The underlying gene is KITLG …”

Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation

“…Genomic DNA was extracted from blood samples of family 1 and a sporadic case using the QIA-amp ® DNA Blood Mini Kit (Qiagen, Shanghai, China). All exons and their flanking intronic sequences of the KITLG gene were amplified by polymerase chain reaction (PCR) as described previously [ 8 ]. Purified PCR products were sequenced directly using an ABI Prism ® 3730 automated sequencer (Applied Biosystems, Foster City, CA, USA).…”

“…Most of the FPHH-causing mutations in KITLG are clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2, and a mutated VTNNV domain may increase the affinity of KITLG to the c-Kit receptor, suggesting that the mutation causes a downstream gain-of-function effect. However, many FPHH families without KITLG mutations have been identified, indicating additional locus heterogeneity for this disorder [ 5 , 8 , 9 ].…”