We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Correspondence |

A Novel Homozygous Missense Mutation in SLURP1 Causing Mal de Meleda With an Atypical Phenotype

Robert Gruber, MD; Hans C. Hennies, PhD; Nikolaus Romani, PhD; Matthias Schmuth, MD
Arch Dermatol. 2011;147(6):748-750. doi:10.1001/archdermatol.2011.138.
Text Size: A A A
Published online


Mal de Meleda (MDM) is a rare autosomal recessive form of keratoderma characterized by sharply demarcated palmoplantar erythema and hyperkeratoses. It usually manifests within the first 2 years of life and takes a slowly progressive course with transgression of the hyperkeratoses to the dorsal aspects of the hands and feet. Associated findings include perioral erythema, hyperkeratotic plaques over the joints, nail abnormalities, hyperhidrosis with malodorous maceration, brachydactyly, and pseudoainhum.13 Mal de Meleda is caused by mutations in SLURP1 (7 different mutations have been detected), encoding the secreted mammalian Ly6/urokinase plasminogen receptor–related protein 1 (SLURP-1), which shows a phylogenetic relationship to snake neurotoxins exhibiting the characteristic 3-finger structure.4 In human keratinocytes, SLURP-1 is an endogenous ligand of the alpha-7-nicotinic acetylcholine receptor and acts as a neuromodulator, likely impacting on epidermal homeostasis and regulating tumor necrosis factor–mediated inflammatory cascades.3

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview


Place holder to copy figure label and caption
Figure 1.

Clinical and histologic mal de Meleda features. A, Diffuse palmar hyperkeratoses and hyperhidrosis. B, Hyperkeratoses of erythematous light gray color with sharp proximal demarcation and transgression to the dorsal aspects of the hands and fingers. C, Hematoxylin-eosin–stained skin sections showing hyperparakeratosis, acanthosis, hypergranulosis, and discrete perivascular lymphocytic infiltrates (original magnification ×100). D, Improved keratoderma (decreased hyperkeratosis and less sharp demarcation) after 6 months of oral acitretin therapy, 20 mg/d.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

SLURP1 mutation analysis, demonstrating a novel homozygous missense mutation p.Pro82Ser (c.244C→T) in exon 3 of the gene, expected to result in altered protein structure.

Graphic Jump Location




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

6 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles