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 acardiac 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 detecting a risk of KCNJ2 gene mutation associated cardiac dysrhythmia in a human subject who has no outward signs of Andersen's Syndrome, comprising:
 a) obtaining a biological sample from the subject;   b) preparing a copy of a KCNJ2 gene from the sample;   c) screening for A440T, T635C, G658A, C880T, G881A, G1127T, and G1135A alterations in the copy of the KCNJ2 gene;   d) identifying the presence or absence of an alteration, and   e) 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 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: a missense mutation, a deletion, an in-frame deletion, and an insertion. 
     
     
         33 . The method of  claim 31 , wherein the identification the presence or absence of a KCNJ2 gene alteration includes assaying and analyzing the sample 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 . The method of  claim 31 , wherein the human subject is an infant. 
     
     
         35 . A method of detecting a risk of KCNJ2 gene mutation associated sudden infant death syndrome in a human infant subject comprising:
 a) obtaining a biological sample from the subject;   b) preparing a copy of a KCNJ2 gene from the sample;   c) screening for A440T, T635C, G658A, C880T, G881A, G1127T, and G1135A alterations in the copy of the KCNJ2 gene;   d) identifying the presence or absence of an alteration, and   e) assessing the subject's risk of sudden infant death associated with mutations in the KCNJ2 gene based on the presence or absence of an alteration in the subject's KCNJ2 gene, wherein if an alteration in the KCNJ2 gene is detected the subject is assessed to have an increased risk for sudden infant death.   
     
     
         36 . The method of  claim 35 , wherein the alteration in the copy of the KCNJ2 gene is selected from the group consisting of: a missense mutation, a deletion, an in-frame deletion, and an insertion. 
     
     
         37 . The method of  claim 35 , 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.