Birbeck Granule Deficiency
A number sign (#) is used with this entry because of evidence that Birbeck granule deficiency is caused by heterozygous mutation in the CD207 gene (604862) on chromosome 2p13. One such patient has been reported.
Clinical FeaturesBirbeck granules (BGs) are rod-shaped cytoplasmic organelles found only in epidermal Langerhans cells (LCs). BGs are thought to be involved in receptor-mediated endocytosis and to participate in the antigen-processing and -presenting function of LCs. Mommaas et al. (1994) reported a healthy 29-year-old Caucasian male whose LCs completely lacked BGs, as determined by electron microscopic studies. The lack of BGs was observed with 5 skin biopsy specimens taken from several places on the individual's body during a period of 2.5 years. Furthermore, a BG-specific monoclonal antibody failed to stain the individual's LCs. Despite the lack of BGs, LCs were present in normal numbers, had all the usual morphologic characteristics, and were CD1A (188370) and human leukocyte antigen (HLA) class II (see 142860) positive. Two observations indicated that these BG-negative LCs had normal antigen-presenting capacity. First, the individual could be sensitized by the hapten diphenylcyclopropenone, and this was accompanied by a strong increase in cell surface expression of HLA class II antigens on LCs, suggesting LC activation. Second, the individual's epidermal cells elicited a normal positive response in an allogeneic mixed epidermal cell lymphocyte reaction. Mommaas et al. (1994) concluded that BGs are not a prerequisite for normal LC function.
Molecular GeneticsVerdijk et al. (2005) identified a heterozygous trp264-to-arg (W264R; 604862.0001) mutation in the CD207 gene, which encodes the protein langerin, in the individual with BG deficiency reported by Mommaas et al. (1994). Expression of langerin with the W264R mutation in fibroblasts induced tubular-like structures that were not recognized by anti-BG antibodies and that lacked the characteristic structural features of BGs.