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Section 3. Genetic Evaluation of Inborn Errors of Immunity
Recommendation 3.1
➤ We recommend single-gene sequencing to test patients with
suspected IEI who have a similarly affected family member with a
known genetic defect or who present with a condition with a defect
in a gene that might not be reliably analyzed using high-throughput
massively parallel sequencing. (S-H)
Recommendation 3.2
➤ We recommend targeted gene panel sequencing including genes
associated with IEI or exome sequencing as an initial step for genetic
diagnosis, when a familial gene defect does not explain the patient's
condition. (S-H)
Recommendation 3.3
➤ We suggest whole genome sequencing of individuals with suspected
IEI and non-immunologic traits or with high suspicion for a noncoding
genetic defect. (C-L)
Recommendation 3.4
➤ We recommend DNA copy number variant (CNV) testing in patients
with IEI with a suspected gene(s) deletion or duplication. (S-H)
Recommendation 3.5
➤ We recommend the American College of Medical Genetics
and Genomics (ACMG) guidelines for evaluating gene variant
pathogenicity. (S-H)
Recommendation 3.6
➤ We recommend familial genetic testing to aid in gene variant
pathogenicity resolution. (S-H)
Recommendation 3.7
➤ We suggest familial genetic testing to ascertain risk of disease in
currently unaffected relatives. (C-L)
Recommendation 3.8
➤ We recommend investigating multiple genetic diagnoses when
a monogenic diagnosis does not explain the patient's clinical
characteristics. (S-M)
Recommendation 3.9
➤ We recommend that genetic testing for patients with IEI can be
ordered by clinicians with expertise in IEI. (S-M)
