Immunodeficiency Due To Defect In Mapbp-Interacting Protein

A number sign (#) is used with this entry because of evidence that this form of primary immunodeficiency is caused by homozygous mutation in the gene encoding the MAPBP-interacting protein (MAPBPIP; 610389) on chromosome 1q22.

Clinical Features

Bohn et al. (2007) described 4 of 15 sibs from a Caucasian Mennonite family who showed a characteristic clinical phenotype associating short stature, hypopigmented skin, coarse facial features, and recurrent bronchopulmonary infections due to Streptococcus pneumoniae. Affected individuals had consistently low peripheral neutrophil counts, with absolute neutrophil counts less than 500 per microliter, although neutrophil maturation in the bone marrow was intact. Compared to healthy sibs, CD8(+) cytotoxic T cells from affected individuals had decreased cytotoxic activity. Structural and functional analysis of patients' immune cells and melanocytes suggested abnormal maturation and function of specialized lysosomes in cytotoxic T cells, melanocytes, and neutrophil granulocytes.

Molecular Genetics

Bohn et al. (2007) performed genomewide linkage analysis in a Caucasian Mennonite family with a primary immunodeficiency syndrome and found significant linkage on chromosome 1q21-q23 between D1S498 and D1S1153. Sequencing of 19 genes in the maximal possible linkage region failed to detect a mutation. Bohn et al. (2007) combined the results of genetic linkage analysis and genomewide transcriptional profiling analysis and found that MAPBPIP (610389) was the only gene located within the crucial region on chromosome 1q21 that was underexpressed by a factor greater than 2 in affected individuals. Sequence analysis revealed that affected individuals were homozygous for a mutation in the 3-prime UTR of exon 4 (610389.0001) that was not found in 100 control alleles or in 34 alleles from healthy Mennonites.