title: FAM65B is a membrane-associated protein of hair cell stereocilia required for hearing.
abstract: In a large consanguineous Turkish kindred with recessive nonsyndromic, prelingual, profound hearing loss, we identified in the gene FAM65B (MIM611410) a splice site mutation (c.102-1G>A) that perfectly cosegregates with the phenotype in the family. The mutation leads to exon skipping and deletion of 52-amino acid residues of a PX membrane localization domain. FAM65B is known to be involved in myotube formation and in regulation of cell adhesion, polarization, and migration. We show that wild-type Fam65b is expressed during embryonic and postnatal development stages in murine cochlea, and that the protein localizes to the plasma membranes of the stereocilia of inner and outer hair cells of the inner ear. The wild-type protein targets the plasma membrane, whereas the mutant protein accumulates in cytoplasmic inclusion bodies and does not reach the membrane. In zebrafish, knockdown of fam65b leads to significant reduction of numbers of saccular hair cells and neuromasts and to hearing loss. We conclude that FAM65B is a plasma membrane-associated protein of hair cell stereocilia that is essential for hearing.
authors: Dr. John T. Macdonald Foundation Department of Human Genetics,John P. Hussman Institute for Human Genomics, and.
authors: Oscar
authors: O
authors: Diaz-Horta
authors: Dr. John T. Macdonald Foundation Department of Human Genetics,John P. Hussman Institute for Human Genomics, andDepartment of Medical Genetics, Erciyes University School of Medicine, Kayseri 38039, Turkey;
authors: Asli
authors: A
authors: Subasioglu-Uzak
authors: Departments of Otolaryngology and.
authors: M'hamed
authors: M
authors: Grati
authors: Department of Biology, University of Miami, Miami, FL 33146; and.
authors: Alexandra
authors: A
authors: DeSmidt
authors: Dr. John T. Macdonald Foundation Department of Human Genetics,John P. Hussman Institute for Human Genomics, and.
authors: Joseph
authors: J
authors: Foster
authors: Dr. John T. Macdonald Foundation Department of Human Genetics,John P. Hussman Institute for Human Genomics, and.
authors: Lei
authors: L
authors: Cao
authors: Dr. John T. Macdonald Foundation Department of Human Genetics,John P. Hussman Institute for Human Genomics, and.
authors: Guney
authors: G
authors: Bademci
authors: Division of Pediatric Genetics, Ankara University School of Medicine, Ankara 06100, Turkey.
authors: Suna
authors: S
authors: Tokgoz-Yilmaz
authors: Division of Pediatric Genetics, Ankara University School of Medicine, Ankara 06100, Turkey.
authors: Duygu
authors: D
authors: Duman
authors: Division of Pediatric Genetics, Ankara University School of Medicine, Ankara 06100, Turkey.
authors: F Basak
authors: FB
authors: Cengiz
authors: Dr. John T. Macdonald Foundation Department of Human Genetics,John P. Hussman Institute for Human Genomics, and.
authors: Clemer
authors: C
authors: Abad
authors: Departments of Otolaryngology and.
authors: Rahul
authors: R
authors: Mittal
authors: Dr. John T. Macdonald Foundation Department of Human Genetics,John P. Hussman Institute for Human Genomics, and.
authors: Susan
authors: S
authors: Blanton
authors: Departments of Otolaryngology and.
authors: Xue Z
authors: XZ
authors: Liu
authors: Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136;
authors: Amjad
authors: A
authors: Farooq
authors: Dr. John T. Macdonald Foundation Department of Human Genetics,John P. Hussman Institute for Human Genomics, and.
authors: Katherina
authors: K
authors: Walz
authors: Department of Biology, University of Miami, Miami, FL 33146; and.
authors: Zhongmin
authors: Z
authors: Lu
authors: Dr. John T. Macdonald Foundation Department of Human Genetics,John P. Hussman Institute for Human Genomics, andDivision of Pediatric Genetics, Ankara University School of Medicine, Ankara 06100, Turkey mtekin@med.miami.edu.
authors: Mustafa
authors: M
authors: Tekin
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006309:Hearing / Q000235:genetics / Q000502:physiology*; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D010375:Pedigree; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012326:RNA Splicing; D059547:Stereocilia / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D014421:Turkey; D015027:Zebrafish
chemical_list: D015815:Cell Adhesion Molecules; D011506:Proteins; C104952:RIPOR2 protein, human
keywords: Mendelian disorder; congenital; deafness; sensorineural; whole-exome sequencing