Sex reversal in an individual with 46,XY karyotype caused by point mutations or deletions in the SRY gene, encoding sex-determining region Y protein.

WHIM syndrome-1 (WHIMS1) is an autosomal dominant immunologic disorder characterized by neutropenia, hypogammaglobulinemia, and warts due to human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis. The susceptibility to HPV is disproportionate compared with other immunodeficiency conditions (summary by Hernandez et al., 2003). Heusinkveld et al. (2019) provided a detailed review of the clinical features, proposed pathogenesis, and possible therapeutic treatments of WHIM syndrome. There is significant phenotypic variation among patients, such that some individuals may have an 'incomplete' form of the disorder in which one or more of the classic tetrad features are not present. In general, the WHIMS phenotype comprises a spectrum of manifestations with variable expressivity. The pathogenesis of WHIMS1 is postulated to result from impaired CXCL12 (600835)-induced internalization of CXCR4, resulting in prolonged receptor presence at the cell surface that likely contributes to amplification of signaling with a gain-of-function effect. Genetic Heterogeneity of WHIM Syndrome See also WHIMS2 (619407), caused by mutation in the CXCR2 gene (146928) on chromosome 2q35.