Genomic coordinate (human 10:24,897,359 DCLRE1C) & (mouse 2:34,251,168 Dclre1c).
Cytoband (human 10p12.1 DCLRE1C) & (mouse 2qB Dclre1c).
Here I present: “Athabascan Severe Combined Immunodeficiency”, Victor McKusick, Mendelian Inheritance in Man’, 1966. (DCLRE1C) icd10=D81.1
Athabascan Severe Combined Immunodeficiency is an autosomal recessive, life-threatening genetic disorder, with a high incidence among Athabascan-speaking Native Americans in the US Southwest. It is characterized by a severe lack of functional T and B cells (T-B-NK+ phenotype) due to mutations in the DCLRE1C gene, often causing sensitivity to ionizing radiation.
ICD-10 Code D81.1 — Athabascan-type severe combined immunodeficiency.
Definition: Athabascan SCID is a genetic immunodeficiency disorder predominantly found among Athabaskan-speaking Native American populations (e.g., Apache, Navajo). It is a T– B– NK+ SCID, meaning:
T cells: Absent or severely reduced
B cells: Absent or severely reduced
NK cells: Normal
This immunodeficiency results in severe susceptibility to infections, often fatal in early childhood without treatment.
Genetics:
Inheritance: Autosomal recessive.
Gene involved: DCLRE1C (Artemis gene, cytoband 10p12.1), which is critical for V(D)J recombination in developing lymphocytes.
Founder effect: Observed in certain Athabascan populations, leading to a higher incidence of this SCID type compared to the general population.
Clinical Features:
Recurrent bacterial, viral, and fungal infections
Failure to thrive in infancy
Chronic diarrhea
Pneumonia, sepsis, or opportunistic infections
Diagnosis
Immunological: Profound lymphopenia (T– B– NK+ profile).
Genetic testing: Mutations in DCLRE1C confirm diagnosis
Newborn screening: TRECs (T-cell receptor excision circles) can identify low T-cell numbers
Treatment:
Hematopoietic stem cell transplantation (HSCT): Curative in many cases
Gene therapy: Investigational, for specific mutations
Supportive care: Immunoglobulin replacement therapy, prophylactic antimicrobials
Epidemiology:
Higher prevalence among Athabaskan-speaking tribes due to founder mutation.
There is evidence Athabascan severe-combined immunodeficiency is caused by mutation in the DNA cross-link repair-1C (DCLRE1C) gene encoded on genomic coordinate 10:24,897,359 and cytoband 10q12.1 in humans.
