A novel <i>ENPP1</i> mutation identified in a multigenerational family affected by Cole disease

“…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 2 …”

Section: Discussionmentioning

confidence: 99%

Congenital hypopigmentation, hyperpigmentation, and punctate palmoplantar keratoderma

Nair

Chang

Evans

2022

Pediatric Dermatology

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“…Since mutations in ENPP1 leading to Cole disease was firstly demonstrated by Eytan et al 2 in 2013, seven mutations in ENPP1 , including p.C120R, p.C133R, p.C149S, p.C164S, p.C176R, p.C177S and p.C177Y, have been reported to be associated with Cole disease 2–4,10 . Of note, all the reported mutations resulting in Cole disease are located within the somatomedin‐B‐like domains (SMB1 or SMB2) of ENPP1 (Figure 3A) interfering with homodimerization of the ENPP1 enzyme which is mediated by its two SMB domains impairing formation of disulphide bridges 3 .…”

Section: Discussionmentioning

confidence: 99%

“…Genetic test is necessary and useful to distinguish Cole disease from other pigmentary disorders (Table 1). 3,4,10,14–19 …”

Section: Discussionmentioning

confidence: 99%

“…Cole disease (OMIM 615522), characterized by guttate hypopigmentation and punctate palmoplantar keratoderma, is a rare autosomal dominant or recessive genodermatosis caused by mutations in ENPP1 1–3 . To date, only a few cases with Cole disease have been reported and most were from Europe 4,5 . In addition to hypopigmentation and punctuate palmoplantar keratosis, Chourabi et al 3 reported 8 patients with Cole disease presented hyperpigmented macules, who were inherited in an autosomal recessive pattern.…”

Section: Introductionmentioning

confidence: 99%

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Hyperpigmentation in a Chinese family with autosomal dominant Cole disease

Wang

2021

Experimental Dermatology

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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.

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Mutation update: Variants of the ENPP1 gene in pathologic calcification, hypophosphatemic rickets, and cutaneous hypopigmentation with punctate keratoderma

Ralph

Levine

Richard³

et al. 2022

Human Mutation

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ENPP1 encodes ENPP1, an ectonucleotidase catalyzing hydrolysis of ATP to AMP and inorganic pyrophosphate (PPi), and an endogenous plasma protein physiologically preventing ectopic calcification of connective tissues. Mutations in ENPP1 have been reported in association with a range of human genetic diseases. In this mutation update, we provide a comprehensive review of all the pathogenic variants, likely pathogenic variants, and variants of unknown significance in ENPP1 associated with three autosomal recessive disorders—generalized arterial calcification of infancy (GACI), autosomal recessive hypophosphatemic rickets type 2 (ARHR2), and pseudoxanthoma elasticum (PXE), as well as with a predominantly autosomal dominant disorder—Cole disease. The classification of all variants is determined using the latest ACMG guidelines. A total of 140 ENPP1 variants were curated consisting of 133 previously reported variants and seven novel variants, with missense variants being the most prevalent (70.0%, 98/140). While the pathogenic variants are widely distributed in the ENPP1 gene of patientsgen without apparent genotype–phenotype correlation, eight out of nine variants associated with Cole disease are confined to the somatomedin‐B‐like (SMB) domains critical for homo‐dimerization of the ENPP1 protein.

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A novel ENPP1 mutation identified in a multigenerational family affected by Cole disease

Cited by 5 publications

References 15 publications

Congenital hypopigmentation, hyperpigmentation, and punctate palmoplantar keratoderma

Congenital hypopigmentation, hyperpigmentation, and punctate palmoplantar keratoderma

Hyperpigmentation in a Chinese family with autosomal dominant Cole disease

Mutation update: Variants of the ENPP1 gene in pathologic calcification, hypophosphatemic rickets, and cutaneous hypopigmentation with punctate keratoderma

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