ClinVar

In a patient with MASP2 deficiency (613791), Stengaard-Pedersen et al. (2003) identified homozygosity for a mutation in exon 3 of the MASP2 gene, resulting in an asp120-to-gly (D120G) substitution (or asp105-to-gly (D105G) in the mature protein) in the CUB1 domain. The patient was in his mid-thirties and had frequent infections and chronic inflammatory disease, including pulmonary fibrosis. The mutation was present in heterozygous state in the patient's parents, brother, and both of his children.

Heterozygosity for the D120G SNP has been shown to occur in Caucasians at a frequency of 3.9% (Thiel et al., 2007). Sokolowska et al. (2015) noted that early reports estimated a frequency of total MASP2 deficiency due a homozygous D120G SNP of 6 in 10,000 (0.0006), whereas subsequent reports indicated that the frequency may be higher, up to 0.0036 or 0.0061.

St. Swierzko et al. (2009) investigated cord blood MASP2 concentrations in a large cohort of 1,788 neonates of Caucasian origin: the median value was 93 ng/ml. Serum MASP2 concentrations correlated with gestational age and birthweight and were significantly lower in premature babies and other pre-term babies compared with term babies. Neonates with MASP2 concentrations below 42 ng/ml were considered to be MASP2-deficient and had a shorter mean gestational age and a higher incidence of prematurity and low birthweight; however, they did not have increased perinatal infections compared to the others. Among 362 samples tested for the D120G SNP, none were homozygous. Heterozygosity for this allele significantly influenced the protein concentration, but not the lectin pathway of complement activity (MBL-MASP2 complex activity). There was no association between this SNP and prematurity, low birthweight, or perinatal infections.

Sokolowska et al. (2015) reported 2 unrelated individuals with pulmonary tuberculosis who were homozygous for the MASP2 D120G polymorphism. One was a 72-year-old man with chronic obstructive pulmonary disease, whereas the other was a 36-year-old woman with no other comorbidities. In addition, 1 of 276 healthy controls was homozygous for the D120G variant. All 3 individuals had low MASP2 serum concentrations and low MBL-MASP2 complex activities. One of the tuberculosis patients also had an MBL2 (154545) mutation (154545.0001) that affected both MBL serum concentration and activity. In a review of published cases including their 2 cases, Sokolowska et al. (2015) noted that 10 patients with MASP2 deficiency and serious diseases, mainly affecting the respiratory tract, had been reported. However, 7 healthy controls homozygous for MASP2 deficiency had also been reported. Thus, the clinical impact of MASP2 deficiency remained uncertain.