The clinical utility of molecular diagnostic testing for primary immune deficiency disorders: a case based review

Abstract

Primary immune deficiency disorders (PIDs) are a group of diseases associated with a genetic predisposition to recurrent infections, malignancy, autoimmunity and allergy. The molecular basis of many of these disorders has been identified in the last two decades. Most are inherited as single gene defects. Identifying the underlying genetic defect plays a critical role in patient management including diagnosis, family studies, prognostic information, prenatal diagnosis and is useful in defining new diseases. In this review we outline the clinical utility of molecular testing for these disorders using clinical cases referred to Auckland Hospital. It is written from the perspective of a laboratory offering a wide range of tests for a small developed country.

Figure 1

Pedigree of a family segregating XLP[17].

Figure 2

Electropherogram of the BTK gene in a normal donor (A) and patient (B). A TGTT deletion in exon 16 leads to a frameshift resulting in a premature stop codon in the BTK gene (g.66795_66798delTTGTT, c.1581_1584delTTTG).

Figure 3

Electropherogram of the CD40L gene in a normal donor (A) and patient (B). A point mutation in exon 5 leads to a premature stop codon in the CD40L (c.475G > A, p.W140X).