Lymphocyte Phenotype of Autosomal Recessive Congenital Ichthyoses Mutated NIPAL4 (Nipal4-nEDD) (NIPALYMPHO)

Phénotype Lymphocytaire Des Ichtyoses congénitales Autosomiques récessives mutées NIPAL4 (Nipal4-nEDD)

Autosomal recessive congenital ichthyoses (ARCI) are monogenic diseases of cornification that correspond to a diffuse abnormality (affecting the entire integument) of epidermal differentiation and therefore of the skin barrier. They manifest as abnormal desquamation (scaling) associated with varying degrees of inflammation (erythema). Around ten genes are currently implicated in ARCI. Nipal 4 is one of these genes, and mutations in it are found in around 1/10 of genotyped ARCI patients.

As part of this follow-up, three Nipal4 ARCI (Nipal4-nEDD) patients followed by the dermatology department of Saint-Louis hospital (Paris) were diagnosed with Sezary syndrome, a rare and serious cutaneous lymphoma (incidence 1/10,000,000), in adulthood (aged 30, 46, and 82). This lymphoma was diagnosed following a change in skin phenotype with worsening erythema, pruritus, and hyperkeratosis. The occurrence of two very rare diseases ( Nipal4-nEDD) and Sezary syndrome) in three patients raises the question of a non-coincidental association. The diagnosis of Sézary syndrome is based on a specific pathological circulating lymphocyte phenotype and is confirmed by skin histology. There is currently no obvious pathophysiological explanation for the concomitant occurrence of these two skin diseases. The blood lymphocyte phenotype of Nipal 4-nEDD patients without Sezary syndrome (SS) is unknown. A first step in investigating the mechanisms that could explain such an association would be to document this baseline lymphocyte phenotype in the Nipal 4-nEDD population without known SS.

Study Overview

• Status: Not yet recruiting
• Conditions: Sezary Syndrome; Ichthyosis, Lamellar
• Intervention / Treatment: Other: blood sampling

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

• Study Contact: Name: Jérôme Lambert, MD PhD; Email: jerome.lambert@u-paris.fr
• Study Contact Backup: Name: Emmanuelle Bourrat, MD; Phone Number: +33 01 42 49 90 90; Email: emmanuelle.bourrat@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (M/F) with autosomal recessive congenital ichthyoses mutated NIPAL4 (Nipal4-nEDD)

Description

Inclusion Criteria:

• Adult patients (> 18 years old)
• ARCI-type ichthyosis with NIPAL4 mutation (Nipal4-nEDD)

Exclusion Criteria:

• Ichthyosis that has not been genotyped or with mutations in different genes
• Patients with concomitant inflammatory, infectious, or hematological conditions
• Individuals subject to legal protection measures or deprived of their liberty by judicial or administrative decision
• Individuals under guardianship/curatorship
• Opposition to the research

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Autosomal recessive congenital ichthyoses (nEDD); Autosomal recessive congenital ichthyoses mutated NIPAL4 (Nipal4-nEDD)	Other: blood sampling; Supplementary blood collection performed during routine venipuncture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of blood lymphocyte phenotype	Description of the complete blood lymphocyte phenotype by immunophenotyping	18 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Sezary Syndrome; nEDD; NIPA like domain containing4 protein, human; Lymphocyte Immunophenotyping
• Additional Relevant MeSH Terms: Neoplasms; Genetic Diseases, Inborn; Immune System Diseases; Neoplasms by Histologic Type; Infant, Newborn, Diseases; Skin Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Congenital Abnormalities; Lymphoma; Skin Diseases, Genetic; Skin Abnormalities; Keratosis; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Sezary Syndrome; Ichthyosis, Lamellar; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: APH251734

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No