Alterations in the long QT syndrome genes KVLQT1 and SCN5A and methods for detecting same
AssigneeUniversity of Utah Research Foundation
InventorsIgor Splawski, Mark T. Keating
Life of this patent
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Abstract
Long QT Syndrome (LQTS) is a cardiovascular disorder characterized by prolongation of the QT interval on electrocardiogram and presence of syncope, seizures and sudden death. Five genes have been implicated in Romano-Ward syndrome, the autosomal dominant form of LQTS. These genes are KVLQT1, HERG, SCN5A, KCNE1 and KCNE2. Mutations in KVLQt1 and KCNE1 also cause the Jervell and Lange-Nielsen syndrome, a form of LQTS associated with deafness, a phenotypic abnormality inherited in an autosomal recessive fashion. Mutational analyzes were used to screen 262 unrelated individuals with LQTS for mutations in the five defined genes. A total of 134 mutations were observed of which eighty were novel.
Claims17
An isolated DNA comprising a sequence of SEQ ID NO:3 as altered by one or more mutations selected from the group consisting of G3340A, C4501G, de14850-4852, G4868T, and G5360A.
An isolated nucleic acid probe specifically hybridizable to a human mutated SCN5A and not to wild-type SCN5A DNA, said mutated SCN5A comprising a mutation of SEQ ID NO:3 selected from the group consisting of G3340A, C4501G, de14850-4852, G4868T, and G5360A.
A method for detecting a mutation in SCN5A said mutation selected from the group consisting of G3340A, C4501G, de14850-4852, G4868T, and G5360A which comprises analyzing a sequence of said SCN5A DNA or RNA from a human sample or analyzing the sequence of cDNA made from mRNA from said sample, for said mutation.
A method of assessing a risk in a human subject for long QT syndrome which comprises screening said subject for a mutation in SCN5A selected from D1114N, L1501V, de1F1617, R1623L, and S1787N by comparing the sequence of said SCN5A or its expression products isolated from a tissue sample of said subject with a wild-type sequence of said SCN5A or its expression products, wherein a mutation selected from D1114N, L1501V, de1F1617, R1623L, and S1787N in the sequence of the subject indicates a risk for long QT syndrome.
A method for diagnosing a mutation which causes long QT syndrome comprising hybridizing a probe which hybridizes to isolated DNA comprising a sequence of SEQ ID NO:
- 3 as altered by one or more mutations selected from the group consisting of G3340A, C4501G, de14850-4852, G4868T, and G5360A and not to wildtype SCN5A DNA, to a patient's sample of DNA or RNA, the presence of a hybridization signal being indicative of long QT syndrome.
A method for diagnosing a mutation which causes long QT syndrome comprising amplifying a region of gene or RNA for SCN5A and sequencing the amplified gene or RNA wherein long QT syndrome is indicated by any one or more mutations selected from the group consisting of G3340A, C4501G, de14850-4852, G4868T, and G5360A.
A method for diagnosing a mutation which causes long QT syndrome comprising identifying a mismatch between a patient's DNA or RNA and a wild-type DNA or RNA probe wherein said probe hybridizes to a region of DNA or RNA wherein said region comprises a mutation of SEQ ID NO:3 selected from the group consisting of G3340A, C4501G, de14850-4852, G4868T, and G5360A.
An isolated DNA encoding an SCN5A polypeptide of SEQ ID NO:4 having a mutation selected from the group consisting of D1114N, L1501V, de1F1617, R1623L, and S1787N.
Dependencies are inferred from the claim text.