Alterations in the long QT syndrome genes KVLQT1 and SCN5A and methods for detecting same
AssigneeUniversity of Utah Research Foundation
InventorsIgor Splawski, Mark 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 analyses 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.
Claims16
An isolated DNA comprising a sequence of SEQ ID NO:1 as altered by one or more mutations selected from the group consisting of C1172T, C1343G, C 1588T, C1697T, C1747T and G1781A.
A method for detecting a mutation in KVLQT1 said mutation selected from the group consisting of C1172T, C1343G, C1588T, C1697T, C1747T and G1781A which comprises analyzing a sequence of said KVLQT1 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 KVLQT1 selected from T3911 , P448R, Q530X, S566F, R583C and R594Q by comparing the sequence of said KVLQT1 or its expression products isolated from a tissue sample of said subject with a wild-type sequence of said KVLQT1 or its expression products, wherein a mutation selected from T3911, P448R, Q530X, S566F, R583C and R594Q 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:1 as altered by one or more mutations selected from the group consisting of C1172T, C1343G, C1588T, C1697T, C1747T and G1781A and not to wild-type KVLQT1 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 KVLQT1 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 C1172T, C1343G, C1588T, C1697T, C1747T and G1781A.
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:1 selected from the group consisting of C1172T, C1343G, C1588T, C1697T, C1747T and G1781A.
An isolated DNA encoding a KVLQT1 polypeptide of SEQ ID NO:2 having a mutation selected from the group consisting of T3911, P448R, Q530X, S566F, R583C and R594Q.
Dependencies are inferred from the claim text.