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AssigneeUniversity of Utah Research Foundation
InventorsNanda A. Singh, Mark F. Leppert, Carole Charlier
Estimating the term…
Generalized idiopathic epilepsies (IGE) cause 40% of all seizures and commonly have a genetic basis. One type of IGE is Benign Familial Neonatal Convulsions (BFNC), a dominantly inherited disorder of newborns. A submicroscopic deletion of chromosome 20q13.3 which co-segregates with seizures in a BFNC family has been identified. Characterization of cDNAs spanning the deleted region identified a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KCNQ1-like class of potassium channels. Nine other BFNC probands were shown to have KCNQ2 mutations including three missense mutations, three frameshifts, two nonsense mutations, and one splice site mutation. A second gene, KCNQ3, was found in a separate BFNC family in which the mutation had been localized to chromosome 8. A missense mutation was found in this gene in perfect cosegregation with the BFNC phenotype in this latter family. This demonstrates that defects in potassium channels can cause epilepsy. Furthermore, some members of one of the BFNC families with a mutation in KCNQ2 also exhibited rolandic epilepsy and one individual with juvenile myoclonic epilepsy has a mutation in an alternative exon of KCNQ3.
A nucleic acid probe which hybridizes specifically to a nucleic acid or its complement under high stringency, said nucleic acid selected from the group consisting of a nucleic acid encoding a protein consisting of the amino acid sequence of SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO:89, SEQ ID NO:91, and SEQ ID NO:96.
A nucleic acid probe which hybridizes specifically to a nucleic acid or its complement under stringent hybridization conditions, wherein said nucleic acid encodes a mutant human KCNQ2 or KCNQ3 polypeptide which causes benign familial neonatal convulsions (BFNC), juvenile myoclonic epilepsy (JME) or rolandic epilepsy and wherein said stringent hybridization conditions prevent said nucleic acid probe from hybridizing to nucleic acid defined by SEQ ID NO:1 or SEQ ID NO:6.
A method for diagnosing the presence of a mutation in human KCNQ2 or KCNQ3 which causes BFNC, JME, or rolandic epilepsy wherein said method is performed by means which identify the presence of sa id mutation.
A method for diagnosing a mutation which causes BFNC, JME or rolandic epilepsy comprising sequencing KCNQ2 or KCNQ3 in a patient s sample of DNA to determine the presence or absence of mutations which cause BFNC, JME or rolandic epilepsy.
A method for diagnosing a mutation which causes BFNC, JME or rolandic epilepsy wherein said method comprises sequencing a KCNQ2 gene or a KCNQ3 gene in a patient s sample of RNA to determine the presence or absence of mutations which cause BFNC, JME or rolandic epilepsy.
A method for diagnosing a mutation which causes BFNC, JME or rolandic epilepsy wherein said method comprises determining KCNQ2 or KCNQ3 sequence in a patient by preparing cDNA from RNA taken from said patient and sequencing said cDNA to determine the presence or absence of mutations which cause BFNC, JME or rolandic epilepsy.
A method of diagnosing the presence of BFNC, JME or rolandic epilepsy by performing in situ hybridization with a probe specific for KCNQ2 or KCNQ3 wherein the presence of only a single copy of either KCNQ2 or KCNQ3 indicates the presence of BFNC, JME or rolandic epilepsy.
A pair of single-stranded DNA primers for determination of a nucleotide sequence of KCNQ2 by a polymerase chain reaction, the sequence of said primers being derived from human chromosome 20q13, wherein the use of said primers in a polymerase chain reaction results in the synthesis of DNA having all or part of the sequence of KCNQ2.
A pair of single-stranded DNA primers for determination of a nucleotide sequence of KCNQ3 by a polylmerase chain reaction, the sequence of said primers being derived from human chromosome 8q24, wherein the use of said primers in a polymerase chain reaction results in the synthesis of DNA having all or part of the sequence of KCNQ3.
A pair of single-stranded DNA primers of clain 29 wherein said pair is selected from:
An isolated DNA comprising DNA having at least 8 consecutive nucleotides of bases 1244-3232 of SEQ ID NO:
An isolated DNA comprising DNA having at least 8 consecutive nucleotides of any one of SEQ ID NOs:100-129.
An isolated DNA comprising DNA having at least 15 consecutive nucleotides of any one of SEQ ID NOs:100-129.
An isolated nucleic acid comprising a sequence selected from any one of SEQ ID NOs:
Dependencies are inferred from the claim text.