Synaptojanin 2 (SYNJ2) Variants And Uses Thereof

A method of treating a patient with a therapeutic agent that treats or inhibits hearing loss, wherein the patient is suffering from hearing loss, the method comprising the steps of:

• determining whether the patient has a Synaptojanin-2 (SYNJ2) predicted loss-of-function variant nucleic acid molecule encoding a human SYNJ2 polypeptide by:
• obtaining or having obtained a biological sample from the patient;
• and
• performing or having performed a genotyping assay on the biological sample to determine if the patient has a genotype comprising the SYNJ2 predicted loss-of-function variant nucleic acid molecule;
• and
• when the patient is SYNJ2 reference, then administering or continuing to administer to the patient the therapeutic agent that treats or inhibits hearing loss in a standard dosage amount;
• and
• when the patient is heterozygous or homozygous for a SYNJ2 predicted loss-of-function variant, then administering or continuing to administer to the patient the therapeutic agent that treats or inhibits hearing loss in an amount that is the same as or greater than a standard dosage amount;
• wherein the presence of a genotype having the SYNJ2 predicted loss-of-function variant nucleic acid molecule encoding the human SYNJ2 polypeptide indicates the patient has an increased risk of developing hearing loss;
• and
• provided that the SYNJ2 predicted loss-of-function variant is not Asn538Lys.

A method of detecting a human Synaptojanin-2 (SYNJ2) variant nucleic acid molecule in a human subject comprising assaying a sample obtained from the human subject to determine whether:

• a genomic nucleic acid molecule in the sample comprises a nucleotide sequence comprising:
• a thymine at a position corresponding to position 89,742 according to SEQ ID NO:2, or the complement thereof;
• or a thymine at a position corresponding to position 99,219 according to SEQ ID NO:3, or the complement thereof;
• an mRNA molecule in the sample comprises a nucleotide sequence comprising a uracil at a position corresponding to position 2,050 according to SEQ ID NO:5, or the complement thereof;
• or
• a cDNA molecule produced from an mRNA molecule in the sample comprises a nucleotide sequence comprising a thymine at a position corresponding to position 2,050 according to SEQ ID NO:7, or the complement thereof.

An isolated alteration-specific probe or alteration-specific primer comprising at least about 15 nucleotides, wherein the alteration-specific probe or alteration-specific primer comprises a nucleotide sequence which is complementary to a portion of a nucleotide sequence encoding a human Synaptojanin-2 (SYNJ2) polypeptide, wherein the portion comprises a position corresponding to:

• position 89,742 according to SEQ ID NO:2, or the complement thereof;
• position 2,050 according to SEQ ID NO:5, or the complement thereof;
• position 2,050 according to SEQ ID NO:7, or the complement thereof;
• or position 99,219 according to SEQ ID NO:3, or the complement thereof.

A molecular complex comprising an alteration-specific primer or an alteration-specific probe hybridized to:

• a genomic nucleic acid molecule comprising a nucleotide sequence encoding a human Synaptojanin-2 (SYNJ2) polypeptide, wherein the alteration-specific primer or the alteration-specific probe is hybridized to:
• a thymine at a position corresponding to position 89,742 according to SEQ ID NO:2, or the complement thereof;
• or a thymine at a position corresponding to position 99,219 according to SEQ ID NO:3, or the complement thereof;
• an mRNA molecule comprising a nucleotide sequence encoding a human Synaptojanin-2 (SYNJ2) polypeptide, wherein the alteration-specific primer or the alteration-specific probe is hybridized to a uracil at a position corresponding to position 2,050 according to SEQ ID NO:5, or the complement thereof;
• or
• a cDNA molecule comprising a nucleotide sequence encoding a human Synaptojanin-2 (SYNJ2) polypeptide, wherein the alteration-specific primer or the alteration-specific probe is hybridized to a thymine at a position corresponding to position 2,050 according to SEQ ID NO:7, or the complement thereof.