A2 Genetics of human (severe) combined immunodeficiency (S)CID


PRINCIPAL INVESTIGATOR
AND CO-INVESTIGATORS
OF THE SUBPROJECT

Bild von PD Dr. med. Klaus Schwarz

Klaus Schwarz

Klaus Schwarz, PD Dr. med.
Institute of Transfusion Medicine, University Ulm
Helmholtzstraße 10
89081 Ulm
Phone: +49 731 150-642
Fax: +49 731 150-575
E-Mail: klaus.schwarz@uni-ulm.de

Bild von Dr. med. Manfred Hönig

Manfred Hönig

Manfred Hönig, Dr. med.
Clinics for Children and Adolescent Medicine, University Hospital Ulm
Eythstraße 24
89075 Ulm
Phone: +49 731 500-57192
Fax: +49 731 500-26685
E-Mail: manfred.hoenig@t-online.de


TITLE OF SUBPROJECT

Genetics of human (severe) combined immunodeficiencies (SCID)


CONDITION/TOPIC

Severe combined Immunodeficiency (SCID) (OMIM #601457, #608971, #269840).


OBJECTIVE(S)

  1. To identifiy SCID entities on the basis of clinical, immunological and genetic analyses
  2. To identify novel genetic causes for SCID
  3. To elaborate the molecular pathophysiology oft these novel SCID entities

SUMMARY

Analyzing the molecular pathophysiology of severe combined immunodeficiency (SCID) has contributed considerably to the knowledge of the human immune system. Presently, mutations in about 20 known genes contribute to human SCID. A significant proportion of SCID patients still remain without a molecular diagnosis, although depending on the immunophenotype all known respective genes have been examined in these patients. In this study in collaboration with a majority of German ID centers, we will identify novel SCID cases on the basis of clinical and immunological data. After exclusion of patients with known defects we will focus on loss of heterozygozity screens and candidate gene sequencing (in consangunous families) and on total exom-/genome sequencing in selected patients to identify the molecular basis of so far unresolved SCID cases. The nature of the gene and its gene product will dictate which molecular methods will have to be used for the pathophysiological analyses. A better understanding of the genetic, immunologic and phenotypic variability of SCID will support the rapid diagnosis and therapy of this life-threatening disorder.