PMID- 18667942
OWN - NLM
STAT- MEDLINE
DCOM- 20090318
LR  - 20211020
IS  - 1537-4505 (Electronic)
IS  - 1531-7129 (Print)
IS  - 1531-7129 (Linking)
VI  - 29
IP  - 6
DP  - 2008 Sep
TI  - In search of the DFNA11 myosin VIIA low- and mid-frequency auditory genetic 
      modifier.
PG  - 860-7
LID - 10.1097/MAO.0b013e3181825651 [doi]
AB  - OBJECTIVES: To evaluate the auditory, vestibular, and retinal characteristics of 
      a large American DFNA11 pedigree with autosomal dominant progressive 
      sensorineural hearing loss that first impacts the low- and mid-frequency auditory 
      range. The pedigree (referred to as the HL2 family) segregates a myosin VIIA 
      (MYO7A) mutation in exon 17 at DNA residue G2164C (MYO7A) that seems to be 
      influenced by a genetic modifier that either rescues or exacerbates the MYO7A 
      alteration. DNA analysis to examine single-nucleotide polymorphisms in 2 
      candidate modifier genes (ATP2B2 and Wolfram syndrome 1 [WFS1]) is summarized in 
      this report. STUDY DESIGN: Family study. RESULTS: The degree of low- and 
      mid-frequency hearing loss in HL2 family members segregating the MYO7A mutation 
      varies from mild to more severe, with approximately the same number of HL2 family 
      members falling at each end of the severity spectrum. The extent of hearing loss 
      in HL2 individuals can vary between family generations. Differences in the degree 
      of hearing loss in MYO7A HL2 family members may be mirrored by vestibular 
      function in at least 2 of these same individuals. The single-nucleotide 
      polymorphisms examined within ATP2B2 and WFS1 did not segregate with the mild 
      versus more severe auditory phenotype. CONCLUSION: The severity of the auditory 
      and vestibular phenotypes in MYO7A HL2 family members may run in parallel, 
      suggesting a common modifier gene within the inner ear. The putative MYO7A 
      genetic modifier is likely to represent a common polymorphism that is not linked 
      tightly to the MYO7A mutation on the MYO7A allele.
FAU - Kallman, Jeremy C
AU  - Kallman JC
AD  - V. M. Bloedel Hearing Research Center, Otolaryngology-HNS Department, University 
      of Washington, Seattle, Washington 98195, USA.
FAU - Phillips, James O
AU  - Phillips JO
FAU - Bramhall, Naomi F
AU  - Bramhall NF
FAU - Kelly, John P
AU  - Kelly JP
FAU - Street, Valerie A
AU  - Street VA
LA  - eng
GR  - P30 DC004661/DC/NIDCD NIH HHS/United States
GR  - P30 DC04661/DC/NIDCD NIH HHS/United States
GR  - R01 DC006901-04/DC/NIDCD NIH HHS/United States
GR  - R03 DC004945/DC/NIDCD NIH HHS/United States
GR  - R01 DC006901-05/DC/NIDCD NIH HHS/United States
GR  - DC04945/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Otol Neurotol
JT  - Otology & neurotology : official publication of the American Otological Society, 
      American Neurotology Society [and] European Academy of Otology and Neurotology
JID - 100961504
RN  - 0 (MYO7A protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Myosin VIIa)
RN  - 0 (wolframin protein)
RN  - EC 3.6.3.8 (Plasma Membrane Calcium-Transporting ATPases)
RN  - EC 3.6.4.1 (Myosins)
RN  - EC 7.2.2.10 (ATP2B2 protein, human)
SB  - IM
MH  - Caloric Tests
MH  - Gene Transfer, Horizontal/genetics
MH  - Hearing Loss, Sensorineural/diagnosis/*genetics
MH  - Humans
MH  - Male
MH  - Membrane Proteins/genetics
MH  - Myosin VIIa
MH  - Myosins/*genetics
MH  - Pedigree
MH  - Plasma Membrane Calcium-Transporting ATPases/genetics
MH  - Point Mutation/genetics
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Severity of Illness Index
MH  - Sex Factors
MH  - Usher Syndromes/diagnosis/*genetics
MH  - Wolfram Syndrome/genetics
PMC - PMC2648351
MID - NIHMS87229
EDAT- 2008/08/01 09:00
MHDA- 2009/03/19 09:00
PMCR- 2009/09/01
CRDT- 2008/08/01 09:00
PHST- 2008/08/01 09:00 [pubmed]
PHST- 2009/03/19 09:00 [medline]
PHST- 2008/08/01 09:00 [entrez]
PHST- 2009/09/01 00:00 [pmc-release]
AID - 10.1097/MAO.0b013e3181825651 [doi]
PST - ppublish
SO  - Otol Neurotol. 2008 Sep;29(6):860-7. doi: 10.1097/MAO.0b013e3181825651.