Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome

<p>Abstract</p> <p>Background</p> <p>Recessive mutations of fibroblast growth factor 3 (FGF3) can cause LAMM syndrome (OMIM 610706), characterized by fully penetrant complete labyrinthine aplasia, microtia and microdontia.</p> <p>Methods</p> <p>We performed a prospective molecular genetic and clinical study of families segregating hearing loss linked to <it>FGF3 </it>mutations. Ten affected individuals from three large Pakistani families segregating <it>FGF3 </it>mutations were imaged with CT, MRI, or both to detect inner ear abnormalities. We also modeled the three dimensional structure of FGF3 to better understand the structural consequences of the three missense mutations.</p> <p>Results</p> <p>Two families segregated reported mutations (p.R104X and p.R95W) and one family segregated a novel mutation (p.R132GfsX26) of <it>FGF3</it>. All individuals homozygous for p.R104X or p.R132GfsX26 had fully penetrant features of LAMM syndrome. However, recessive p.R95W mutations were associated with nearly normal looking auricles and variable inner ear structural phenotypes, similar to that reported for a Somali family also segregating p.R95W. This suggests that the mild phenotype is not entirely due to genetic background. Molecular modeling result suggests a less drastic effect of p.R95W on FGF3 function compared with known missense mutations detected in fully penetrant LAMM syndrome. Since we detected significant intrafamilial variability of the inner ear structural phenotype in the family segregating p.R95W, we also sequenced <it>FGF10 </it>as a likely candidate for a modifier. However, we did not find any sequence variation, pointing out that a larger sample size will be needed to map and identify a modifier. We also observed a mild to moderate bilateral conductive hearing loss in three carriers of p.R95W, suggesting either a semi-dominant effect of this mutant allele of <it>FGF3</it>, otitis media, or a consequence of genetic background in these three family members.</p> <p>Conclusions</p> <p>We noted a less prominent dental and external ear phenotype in association with the homozygous p.R95W. Therefore, we conclude that the manifestations of recessive <it>FGF3 </it>mutations range from fully penetrant LAMM syndrome to deafness with residual inner ear structures and, by extension, with minimal syndromic features, an observation with implications for cochlear implantation candidacy.</p

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Women of the American Otological Society

© 2018 Otology Neurotology, Inc. Objective:To describe the history of women in the American Otological Society (AOS).Methods:Biographies of the early women of the AOS were compiled through review of the AOS transactions, their published scholarship, newspaper articles, and memorials. Interviews were conducted with the only two women to have led the society and also with former colleagues and family members of pioneering AOS women members who are no longer with us. The evolving gender composition of the society over time was researched from AOS membership lists and compared with data on surgical workforce composition from multiple sources such as the Association of American Medical Colleges, Accreditation Council for Graduate Medical Education, American Medical Association, and the American Academy of Otolaryngology-Head and Neck Surgery.Results:Although American women specialized in otology as far back as 1895, the first woman to be invited to join the AOS as Associate member in 1961 was Dorothy Wolff, PhD. The first female full member was otologic surgeon LaVonne Bergstrom, M.D., who was elected in 1977, 109 years after the foundation of the Society. As of 2017, only two women have served as AOS President. The first was Aina Julianna Gulya, M.D., who took office during the 133rd year in 2001. At the time of the sesquicentennial (2017), 7.5% of AOS members are women including three of eight who serve on the AOS Council. This compares with 15.8% of women among the otolaryngology workforce and a growing 10.9% representation among those who have earned subcertification in neurotology.Conclusion:Gender disparities remain in the AOS, but both participation and scholarly contributions by women in otology have grown substantially since the society\u27s inception 150 years ago, and particularly in the 21st century. Increasing the presence of women in leadership provides role models and mentorship for the future