Methods for Assessing Risk for Cardiac Dysrythmia in a Human Subject

Abstract

The present invention relates to methods for assessing the risk of a patient for developing a potentially fatal cardiac dysrhythmia and for diagnosing Andersen's Syndrome. A tissue sample from a patient is obtained and the DNA or proteins of the sample isolated. From the DNA and protein isolates the sequence of the KCNJ2 gene or the Kir2.1 polypeptide can be obtained. The KCNJ2 gene or the Kir2.1 can be screened for alteration as compared to the wile-type sequence. An alteration in a copy of the KCNJ2 gene or a Kir2.1 polypeptide indicates that the patient has a high risk for developing a cardiac dysrhythmia and can be diagnosed with Andersen's Syndrome. The invention also related to isolated nucleic acid molecules with one or more alterations as compared to the wild-type sequence.

1 .- 30 . (canceled) 
     
     
         31 . A method of assessing a risk in a human subject for cardiac dysrhythmia associated with mutations in the KCNJ2 gene, wherein the human subject has no outward signs of Andersen's Syndrome, comprising:
 a) screening for each of the A44OT, T635C, G658A, C880T, G881A, G1127T, and G1135A alterations in a copy of the KCNJ2 gene of the human subject by obtaining a biological sample from the subject and assaying and analyzing the sample for the presence or absence of an alteration, and   b) identifying such alteration, wherein the alteration in a copy of the KCNJ2 gene of the human subject indicates a risk for cardiac dysrhythmia in the human subject   c) assessing the subject's risk of cardiac dysrhythmia associated with mutations in the KCNJ2 gene based on the presence or absence of an alteration in a the subject's KCNJ2 gene, wherein if an alteration in the KCNJ2 gene is detected the subject is assessed an increased risk for cardiac dysrhythmia.   
     
     
         32 . The method of  claim 31 , wherein the alteration in the copy of the KCNJ2 gene is selected from the group consisting of missense mutation, a deletion, an in-frame deletion, and an insertion. 
     
     
         33 . The method of  claim 31 , wherein the assaying and analyzing of the sample is accomplished utilizing at least one technique selected from the group consisting of: Northern blot analysis, PCR amplification, RNase protection, monoclonal antibodies, Western blots, and ELISA assay. 
     
     
         34 . A method of assessing risk for sudden infant death associated with mutations in the KCNJ2 gene, in an infant human subject comprising:
 a) screening for each of the A44OT, T635C, G658A, C880T, G881A, G1127T, and G1135A alterations in a copy of the KCNJ2 gene of the infant human subject by obtaining a biological sample from the subject and assaying and analyzing the sample for the presence or absence of an alteration; and   b) identifying the alteration in the KCNJ2 gene, wherein an alteration in a copy of the KCNJ2 gene of the infant human subject indicates a risk for a positive diagnosis for sudden infant death in the infant human subject   c) assessing the infant human subject's risk of sudden infant death based on the presence or absence of an alteration in a the subject's KCNJ2 gene, wherein if an alteration in the KCNJ2 gene is detected, the infant human subject is assessed an increased risk for sudden infant death.   
     
     
         35 . The method of  claim 34 , wherein the alteration in the copy of the KCNJ2 gene is selected from the group consisting of missense mutation, a deletion, an in-frame deletion, and an insertion. 
     
     
         36 . The method of  claim 34 , wherein the assaying and analyzing of the sample is accomplished utilizing at least one technique selected from the group consisting of: Northern blot analysis, PCR amplification, RNase protection, monoclonal antibodies, Western blots, and ELISA assay. 
     
     
         37 . A method of assessing risk of an infant human subject for sudden infant death associated with mutations in the KCNJ2 gene, comprising:
 a) screening for each of the A44OT, T635C, G658A, C880T, G881A, G1127T, and G1135A alterations in a copy of the KCNJ2 gene of a parent or sibling of the infant human subject by obtaining a biological sample from the parent or sibling of the infant human subject and assaying and analyzing the sample for the presence or absence of an alteration; and   b) identifying the alteration in the KCNJ2 gene, wherein an alteration in a copy of the KCNJ2 gene of the parent or sibling of the infant human subject indicates a risk for a positive diagnosis for sudden infant death in the infant human subject;   c) assessing the infant human subject's risk of sudden infant death based on the presence or absence of an alteration in a the subject's KCNJ2 gene, wherein if an alteration in the KCNJ2 gene is detected in the parent or sibling of the infant human subject, the infant human subject is assessed an increased risk for sudden infant death.   
     
     
         38 . The method of  claim 37 , wherein the alteration in the copy of the KCNJ2 gene is selected from the group consisting of missense mutation, a deletion, an in-frame deletion, and an insertion. 
     
     
         39 . The method of  claim 37 , wherein the assaying and analyzing of the sample is accomplished utilizing at least one technique selected from the group consisting of: Northern blot analysis, PCR amplification, RNase protection, monoclonal antibodies, Western blots, and ELISA assay.