Genetic and Clinical Characterization of Type 1 and 2 Narcolepsy in Adult and Pediatric Black and North African Populations

Narcolepsy type 1 (NT1) is a neurological disease characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. It is caused by the loss of neurons located in the lateral hypothalamus leading to a sudden deficiency of a neuropeptide hypocretin/orexin involved in the functions of sleep and wakefulness but also food intake and metabolism. NT1 is diagnosed by the presence of EDS and cataplexies or in the absence of cataplexies but with documented hypocretin/orexin deficiency measured in the cerebrospinal fluid (CSF). Other cases without cataplexy (and without orexin deficiency) are classified as narcolepsy type 2 (NT2).

Although narcolepsy has been widely studied in different populations, there is a lack of knowledge about the genetic and clinical characteristics of people of Black and North African descent.

In Caucasian populations, NT1 is associated with specific major histocompatibility complex (MHC) alleles, particularly HLA-DQB1*06:029. However, recent observations in African American populations have indicated a different clinical presentation. Notably, earlier onset, increased prevalence of atypical symptoms, greater prevalence of narcolepsy without cataplexy, and low cerebrospinal fluid orexin levels have been reported. Specifically, the DQB103:01 allele has been associated with NT1 in African Americans. Additionally, in African populations, a specific mutation called DQB103:19 has been identified within the DQB103:0112 allele.

Genome-wide association studies (GWAS) have proven to be of major interest in identifying genetic variations associated with complex disorders. However, the majority of GWAS on narcolepsy have focused on non-African populations. Carrying out a GWAS in black and North African populations is able to provide new information on the genetic architecture of NT1 and NT2 and highlight specific risk factors in this particularly exposed population.

In conclusion, better understanding the genetic and clinical heterogeneity of NT1 and NT2 in black and North African populations is crucial to advance our knowledge of this disease and adapt targeted diagnostic and therapeutic approaches to specific populations. The present study aims to contribute significantly to the understanding of pediatric and adult narcolepsy and to facilitate more personalized and effective interventions for individuals of African descent.

Although narcolepsy has been widely studied in different populations, there is a lack of knowledge about the genetic and clinical characteristics of people of Black and North African descent.

Inclusion criteria

Narcolepsy patients:

• Individuals of black and North African origin diagnosed with NT1 or NT2.
• Age ≥ 6 years
• Clinical confirmation of narcolepsy according to the criteria of the International Classification of Sleep Disorders (ICSD-3).
• Signature of informed consent by the adult patient or both holders of parental authority for minor patients.

Control subjects:

• Volunteers without pathology related to the study from the same ethnic or related groups with the aim of reaching two matched control subjects for each case.
• Age ≥ 6 years
• Signature of informed consent by the adult subject or both holders of parental authority for minor subjects.

Exclusion criteria

• Individuals unable to understand the protocol or unwilling to participate.