Hyperpigmentation in a Chinese family with autosomal dominant Cole disease

Abstract

Cole disease (OMIM 615522), caused by mutations in ENPP1, is a rare autosomal dominant or recessive genodermatosis characterized by guttate hypopigmentation and punctate palmoplantar keratoderma. To date, a few cases with autosomal recessive inheritance had been reported with hyperpigmentation. The aim of this case report was to investigate the molecular basis of individuals with hyperpigmentation, hypopigmentation and punctate keratoderma in a Chinese family. A Chinese pedigree of suspected Cole disease with hyperpigmentation was subjected to mutation detection in the ENPP1 gene. All exons of the ENPP1 gene and adjacent exon‐intron border sequences were amplified using polymerase chain reaction and directly sequenced. Three‐dimensional (3D) models of the wild‐type and mutated ENPP1 proteins were predicted by PyMOL viewer. Both of the proband and his affected father carried a heterozygous missense mutation p.C176R in ENPP1. In silico modelling of the ENPP1 wild‐type and ENPP1 with the p.C176R mutation showed the residue Arg‐176 disturbed the fold of the loop conformation. Based on clinical and genetic findings, a diagnosis of Cole disease was made. We identified a heterozygous mutation, p.C176R, in the ENPP1 gene in a Chinese family with Cole disease. This study clearly showed that hyperpigmentation could also occur in Cole disease in cases with autosomal dominant inheritance. Our data expand the phenotypic spectrum of ENPP1 mutations underlying Cole disease.

Congenital hypopigmentation, hyperpigmentation, and punctate palmoplantar keratoderma

“…Cole disease classically presents with hypopigmented macules limited to the extremities and punctate palmoplantar keratoderma (PPK) 1,2 . Hyperpigmented macules have been noted in several cases of autosomal recessive transmission of Cole disease and recently in a family affected by an autosomal dominant transmission of a variant as well 3 . Less frequently, cutaneous calcification has been reported 2,4 .…”

“…1,2 Hyperpigmented macules have been noted in several cases of autosomal recessive transmission of Cole disease and recently in a family affected by an autosomal dominant transmission of a variant as well. 3 Less frequently, cutaneous calcification has been reported. 2,4 Cole disease historically lacks any extracutaneous manifestations.…”

Cole disease due to a novel pathogenic variant in the ENPP1 gene

“…Editor, Cole disease (COLED, MIM #615522) is a rare genodermatosis characterized by dyspigmentation and punctate palmoplantar keratoderma (PPPK) of which only 13 families have been reported in the literature to date. [1][2][3][4][5][6][7][8] We report an Indian family with Cole disease with a novel pathogenic variant in ENPP1 in the somatomedin-B-like2 (SMB2) domain.…”

“…[1][2][3][4][5][6][7] Dupilumab, a monoclonal antibody for the treatment of AD, targets the IL-4 receptor subunit a, shared by IL-4 and IL-13 receptors. 8 Dupilumab effectiveness in AA was evaluated in a phase IIa clinical trial including 40 subjects receiving weekly subcutaneous dupilumab 300 mg, and 20 subjects receiving placebo. 9 After 48 weeks of treatment, the percentage of patients achieving the improvement in Severity of Alopecia Tool (SALT) score of 30% (SALT30)/SALT50/SALT75 was 32.5%, 22.5% and 15% respectively.…”

A 3-month-old Infant with Mottled Hypo- and Hyper-pigmented Patches on the Extremities: A Quiz

“…Moreover, insulin regulates melanosome transfer from melanocytes to keratinocytes by the proteinase-activated receptor 2 (PAR-2) and mutation in this signalling causes a decrease in melanosome transfer ( 6 ). Systemic involvement associated with abnormal insulin regulation, such as diabetes, has not been reported in patients with Cole disease ( 7 ).…”