UMIN-CTR Clinical Trial

Public title

Deciphering the pathogenesis of skin disorders driven by genetic alterations via multi-omics analysis

Acronym

Deciphering the pathogenesis of skin disorders driven by genetic alterations via multi-omics analysis

Scientific Title

Deciphering the pathogenesis of skin disorders driven by genetic alterations via multi-omics analysis

Scientific Title:Acronym

Deciphering the pathogenesis of skin disorders driven by genetic alterations via multi-omics analysis

Region

Japan

Condition

genodermatoses

Classification by specialty

Dermatology

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

Patients will include: (i) monogenic disorders that manifest with cutaneous symptoms; (ii) conditions for which a genetic background or predisposition is scientifically considered likely to contribute to disease onset; (iii) conditions for which acquired (somatic) genetic changes are scientifically considered likely to contribute to disease onset; and (iv) undiagnosed disorders with cutaneous manifestations in which a genetic predisposition is inferred but the phenotype does not match any known entity. In these patients, we will comprehensively interrogate congenital (germline) and acquired (somatic) genetic alterations, as well as lesion-specific somatic changes in gene expression, using a suite of multi-omics technologies, including whole-exome sequencing (WES), whole-genome sequencing (WGS), targeted exome sequencing, transcriptome (RNA-seq) analysis, SNP array genotyping, EPIC methylation array analysis, ATAC-seq, single-cell analyses, mass-spectrometry-based proteomics, lipidomics, and exosome analyses, with the primary objective of identifying the genetic alterations that underlie disease onset.

Basic objectives2

Others

Basic objectives -Others

Discovery of novel causative genes
Identification of previously unrecognized diseases
Detection of pathogenic genetic alterations
Assessment of genotype-phenotype correlations
Evaluation of recurrence rates

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Identification of genetic alterations underlying skin diseases.

Key secondary outcomes

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients (and their relatives) diagnosed with any of the following conditions that manifest with symptoms involving the skin, including cutaneous adnexa (nails, hair, teeth) and mucosa (e.g., lips, oral cavity):
(i) monogenic disorders;
(ii) conditions for which a genetic background/predisposition is scientifically considered likely to contribute to disease onset;
(iii) conditions for which acquired (somatic) genetic changes are scientifically considered likely to contribute to disease onset;
(iv) undiagnosed disorders with cutaneous manifestations in which a genetic predisposition is inferred but the phenotype does not match any known disease.

Key exclusion criteria

(1) Patients with dementia or psychiatric disorders requiring treatment, or patients in a comatose state.
(2) Patients whom the principal investigator judges to be unsuitable for inclusion in this study.

Target sample size

3600

Name of lead principal investigator

1st name	Akiharu
Middle name
Last name	Kubo

Organization

Kobe University

Division name

Graduate School of Medicine

Zip code

650-0017

Address

7-5-1 Kusunoki-cho, Chuo-ku, Kobe

TEL

078-382-5111

Email

akiharu@med.kobe-u.ac.jp

Name of contact person

1st name	Ai
Middle name
Last name	Yoshioka

Organization

Kobe University

Division name

Graduate School of Medicine

Zip code

650-0017

Address

7-5-1 Kusunoki-cho, Chuo-ku, Kobe

TEL

078-382-5111

Homepage URL

Email

aiichi39@med.kobe-u.ac.jp

Institute

Kobe University

Institute

Department

Personal name

Organization

JSPS

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Kobe University Hospital CTRC

Address

7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017

Tel

078-382-5111

Email

chiken@med.kobe-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2025

Year

10

Month

21

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2023

Year

04

Month

17

Day

Date of IRB

2023

Year

04

Month

21

Day

Anticipated trial start date

2023

Year

04

Month

21

Day

Last follow-up date

2032

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

The following analyses will be performed:
(i) Genetic analyses of genomic DNA derived from blood (or from saliva if venipuncture is difficult), including targeted exome sequencing, Sanger sequencing, TaqMan assays, whole-exome sequencing (WES), whole-genome sequencing (WGS), SNP array genotyping, quantitative real-time PCR (qPCR), EPIC DNA methylation array analysis, ATAC-seq, and methylation-specific PCR (MSP), among others.
(ii) Genetic analyses of genomic DNA derived from lesional and non-lesional tissue samples, or from primary cultured cells established from such tissues, including targeted exome sequencing, Sanger sequencing, TaqMan assays, WES, WGS, SNP array genotyping, qPCR, EPIC DNA methylation array analysis, ATAC-seq, and MSP, among others.
(iii) Genetic analyses of sperm-derived genomic DNA, including Sanger sequencing, TaqMan assays, SNP array genotyping, qPCR, digital PCR, and targeted exome sequencing, among others.
(iv) RNA analyses of RNA derived from blood, from lesional and non-lesional tissue samples, or from primary cultured cells established from such tissues, including transcriptome (RNA-seq) analysis and qPCR, among others.
(v) Comprehensive omics analyses of blood, lesional and non-lesional tissue samples, or primary cultured cells established from such tissues, including mass spectrometry-based analyses, mass spectrometry imaging (MSI), spatial transcriptomics, single-cell analyses, proteomics, lipidomics, and exosome analyses, among others.
(vi) Tissue-level analyses of lesional and non-lesional tissue samples targeting molecules involved in metabolic pathways, signaling pathways, and molecular interactions related to identified or candidate causative/etiologic genes and their products, including histochemical staining, immunohistochemistry (IHC), immunofluorescence (IF), and in situ hybridization (ISH).

Registered date

2025

Year

10

Month

21

Day

Last modified on

2025

Year

10

Month

21

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000068035