There are several syndromes with abnormal susceptibility to infections which seem to have a genetic basis, but for which no linkage studies or gene candidate evaluations have been done. In collaboration with investigators at NIAID, particularly Dr. S. Holland, we have undertaken studies to elucidate the genetic cause of two disorders. The first is a newly recognized susceptibility to Mycobacterium Avium infections, occurring in males in an extended kindred in with an apparently X-linked inheritance pattern. We have determined that the monocytes of affected individuals fail to produce IL-12, an important inducer of interferon which in turn activates macrophages to kill ingested mycobacteria. A carrier test for females has been designed and linkage studies are under way. A second disease under study is the Hyper IgE syndrome, also known as Job's syndrome, in which affected individuals are susceptible to recurrent skin and lung infections and have extreme elevations of IgE. In evaluating sporadic patients and families with multiple affected members we have noted that features of the syndrome other than the susceptibiity to infection exist, and that the mode of inheritance is autodomal dominant with variable expressivity and penetrance. A genome-wide linkage search is planned.
| Vogt, Guillaume; Chapgier, Ariane; Yang, Kun et al. (2005) Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations. Nat Genet 37:692-700 |
| Grimbacher, Bodo; Holland, Steven M; Puck, Jennifer M (2005) Hyper-IgE syndromes. Immunol Rev 203:244-50 |
| Rao, V Koneti; Dugan, Faith; Dale, Janet K et al. (2005) Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome. Br J Haematol 129:534-8 |
| Maric, Irina; Pittaluga, Stefania; Dale, Janet K et al. (2005) Histologic features of sinus histiocytosis with massive lymphadenopathy in patients with autoimmune lymphoproliferative syndrome. Am J Surg Pathol 29:903-11 |
| Renner, Eleonore D; Puck, Jennifer M; Holland, Steven M et al. (2004) Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity. J Pediatr 144:93-9 |
| Tock, Christine L; Holland, Steven M; Puck, Jennifer M et al. (2004) A man with distinctive facial features and recurrent pyoderma, pneumonia, and skeletal fractures. J Am Acad Dermatol 50:627-9 |
| Notarangelo, Luigi; Casanova, Jean-Laurent; Fischer, Alain et al. (2004) Primary immunodeficiency diseases: an update. J Allergy Clin Immunol 114:677-87 |
| Hay, Beverly N; Martin, Julie E; Karp, Barbara et al. (2004) Familial immunodeficiency with cutaneous vasculitis, myoclonus, and cognitive impairment. Am J Med Genet A 125:145-51 |
| Puck, Jennifer M; Straus, Stephen E (2004) Somatic mutations--not just for cancer anymore. N Engl J Med 351:1388-90 |
| Matsuzaki, Hajime; Loi, Halina; Dong, Shoulian et al. (2004) Parallel genotyping of over 10,000 SNPs using a one-primer assay on a high-density oligonucleotide array. Genome Res 14:414-25 |
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