Presentation is loading. Please wait.

Presentation is loading. Please wait.

Atteeq U. Rehman, Regie Lyn P. Santos-Cortez, Robert J

Published byChristian Walters Modified over 5 years ago

Similar presentations

Presentation on theme: "Atteeq U. Rehman, Regie Lyn P. Santos-Cortez, Robert J"— Presentation transcript:

1 Mutations in TBC1D24, a Gene Associated With Epilepsy, Also Cause Nonsyndromic Deafness DFNB86 
Atteeq U. Rehman, Regie Lyn P. Santos-Cortez, Robert J. Morell, Meghan C. Drummond, Taku Ito, Kwanghyuk Lee, Asma A. Khan, Muhammad Asim R. Basra, Naveed Wasif, Muhammad Ayub, Rana A. Ali, Syed I. Raza, Deborah A. Nickerson, Jay Shendure, Michael Bamshad, Saima Riazuddin, Neil Billington, Shaheen N. Khan, Penelope L. Friedman, Andrew J. Griffith, Wasim Ahmad, Sheikh Riazuddin, Suzanne M. Leal, Thomas B. Friedman  The American Journal of Human Genetics  Volume 94, Issue 1, Pages (January 2014) DOI: /j.ajhg Copyright © 2014 The American Society of Human Genetics Terms and Conditions

2 Figure 1 Refinement of the DFNB86 Linkage Interval
The thick vertical bar represents human chromosome 16p. The linkage interval for the deafness segregating in each of the four families is indicated by a thin vertical bar. The gray shaded region highlights the DFNB86 linkage interval shared by the four families. The American Journal of Human Genetics  , DOI: ( /j.ajhg ) Copyright © 2014 The American Society of Human Genetics Terms and Conditions

3 Figure 2 Four Families in which Deafness Cosegregates with Missense Mutations in TBC1D24 (A) Profound deafness in three families cosegregates with the c.208G>T (p.Asp70Tyr) variant in TBC1D24. Representative chromatograms from wild-type and mutant sequences are shown. Altered nucleotides and affected residues are highlighted in gray. Genotypes of the participating family members are shown below each symbol in single-letter amino acid nomenclature. Individuals diagnosed with either seizures or epilepsy are highlighted by a gray rectangle. In family PKDF799, 10 of 11 deaf individuals have no history of seizures. Deaf female IV-13 had febrile seizures at the age of 8 years. In family DEM4587, there is no history of seizures in any of the eight clinically investigated family members, indicated by asterisks. Clinical re-evaluation of families DEM4221 and DEM4476 was not possible. (B) Deaf individuals from family DEM4476 are homozygous for the c.878G>C (p.Arg293Pro) variant in TBC1D24, whereas normal-hearing parents and siblings of affected family members are heterozygous carriers of this mutation. The American Journal of Human Genetics  , DOI: ( /j.ajhg ) Copyright © 2014 The American Society of Human Genetics Terms and Conditions

4 Figure 3 Structure of TBC1D24 and Amino Acid Conservation of the Affected TBC1D24 Residues (A) ClustalW2 alignment of TBC1D24 orthologs shows that the two DFNB86-associated mutations affect conserved residues (red font). Amino acid residue identity and similarity percentages were calculated for full-length TBC1D24. (B) Graphic representation of TBC1D24 structure (left) and its encoded protein (right). The red bar above the TLDc domain represents the epitope for the commercial antibody (Abcam, ab101933) that we used in Figure 4. DFNB86-associated mutations are shown above the diagram, and epilepsy-associated mutations are shown below. Tall and short gray boxes represent coding exons and UTRs of the transcribed gene, respectively. Horizontal lines joining the gray boxes denote introns. The longest isoform of TBC1D24 was used as the reference sequence for mutation nomenclature (RefSeq NM_ and NP_ ). c. 1544C>T (p.Ala515Val) is renamed here according to the longest isoform but was originally reported as c.1526C>T (p.Ala509Val) on the basis of a shorter isoform of TBC1D24 (Falace et al.24). The American Journal of Human Genetics  , DOI: ( /j.ajhg ) Copyright © 2014 The American Society of Human Genetics Terms and Conditions

5 Figure 4 TBC1D24 Is Found in Spiral Ganglion Neurons of the Mouse Inner Ear (A) TBC1D24 antibody binds to spiral ganglion cells in the P30 cochlea. (B) The corresponding signal is absent in a control experiment with no added primary antibody. (C) A higher-magnification image reveals TBC1D24 antibody binding to the cell body and axonal projections of spiral ganglion. Scale bars in (A) and (B) represent 40 μm, whereas that in (C) represents 10 μm. The American Journal of Human Genetics  , DOI: ( /j.ajhg ) Copyright © 2014 The American Society of Human Genetics Terms and Conditions

Download ppt "Atteeq U. Rehman, Regie Lyn P. Santos-Cortez, Robert J"

Similar presentations

A Mutation in HOXA2 Is Responsible for Autosomal-Recessive Microtia in an Iranian Family  Fatemeh Alasti, Abdorrahim Sadeghi, Mohammad Hossein Sanati,

A Mutation in HOXA2 Is Responsible for Autosomal-Recessive Microtia in an Iranian Family  Fatemeh Alasti, Abdorrahim Sadeghi, Mohammad Hossein Sanati,
Homozygosity Mapping Reveals Mutations of GRXCR1 as a Cause of Autosomal- Recessive Nonsyndromic Hearing Impairment  Margit Schraders, Kwanghyuk Lee, Jaap.

Homozygosity Mapping Reveals Mutations of GRXCR1 as a Cause of Autosomal- Recessive Nonsyndromic Hearing Impairment  Margit Schraders, Kwanghyuk Lee, Jaap.
Loss-of-Function Mutations of ILDR1 Cause Autosomal-Recessive Hearing Impairment DFNB42  Guntram Borck, Atteeq Ur Rehman, Kwanghyuk Lee, Hans-Martin Pogoda,

Loss-of-Function Mutations of ILDR1 Cause Autosomal-Recessive Hearing Impairment DFNB42  Guntram Borck, Atteeq Ur Rehman, Kwanghyuk Lee, Hans-Martin Pogoda,
Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness  Sedigheh.

Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness  Sedigheh.
Autosomal Recessive Nonsyndromic Neurosensory Deafness at DFNB1 Not Associated with the Compound-Heterozygous GJB2 (Connexin 26) Genotype M34T/167delT 

Autosomal Recessive Nonsyndromic Neurosensory Deafness at DFNB1 Not Associated with the Compound-Heterozygous GJB2 (Connexin 26) Genotype M34T/167delT 
Mutations in FLVCR2 Are Associated with Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome (Fowler Syndrome)  Esther Meyer, Christopher.

Mutations in FLVCR2 Are Associated with Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome (Fowler Syndrome)  Esther Meyer, Christopher.
Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering  M. Hashim Raza, Rafael Mattera, Robert.

Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering  M. Hashim Raza, Rafael Mattera, Robert.
Tracy Dixon-Salazar, Jennifer L. Silhavy, Sarah E. Marsh, Carrie M

Tracy Dixon-Salazar, Jennifer L. Silhavy, Sarah E. Marsh, Carrie M
A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa  Goranka Tanackovic, Adriana Ransijn,

A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa  Goranka Tanackovic, Adriana Ransijn,
Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A

Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A
Mutations in TPRN Cause a Progressive Form of Autosomal-Recessive Nonsyndromic Hearing Loss  Yun Li, Esther Pohl, Redouane Boulouiz, Margit Schraders,

Mutations in TPRN Cause a Progressive Form of Autosomal-Recessive Nonsyndromic Hearing Loss  Yun Li, Esther Pohl, Redouane Boulouiz, Margit Schraders,
Functional Null Mutations of MSRB3 Encoding Methionine Sulfoxide Reductase Are Associated with Human Deafness DFNB74  Zubair M. Ahmed, Rizwan Yousaf,

Functional Null Mutations of MSRB3 Encoding Methionine Sulfoxide Reductase Are Associated with Human Deafness DFNB74  Zubair M. Ahmed, Rizwan Yousaf,
LTBP3 Pathogenic Variants Predispose Individuals to Thoracic Aortic Aneurysms and Dissections  Dong-chuan Guo, Ellen S. Regalado, Amelie Pinard, Jiyuan.

LTBP3 Pathogenic Variants Predispose Individuals to Thoracic Aortic Aneurysms and Dissections  Dong-chuan Guo, Ellen S. Regalado, Amelie Pinard, Jiyuan.
TBC1D24, an ARF6-Interacting Protein, Is Mutated in Familial Infantile Myoclonic Epilepsy  Antonio Falace, Fabia Filipello, Veronica La Padula, Nicola.

TBC1D24, an ARF6-Interacting Protein, Is Mutated in Familial Infantile Myoclonic Epilepsy  Antonio Falace, Fabia Filipello, Veronica La Padula, Nicola.
PTPN11 Mutations in Noonan Syndrome: Molecular Spectrum, Genotype-Phenotype Correlation, and Phenotypic Heterogeneity  Marco Tartaglia, Kamini Kalidas,

PTPN11 Mutations in Noonan Syndrome: Molecular Spectrum, Genotype-Phenotype Correlation, and Phenotypic Heterogeneity  Marco Tartaglia, Kamini Kalidas,
Mutations in KARS, Encoding Lysyl-tRNA Synthetase, Cause Autosomal-Recessive Nonsyndromic Hearing Impairment DFNB89  Regie Lyn P. Santos-Cortez, Kwanghyuk.

Mutations in KARS, Encoding Lysyl-tRNA Synthetase, Cause Autosomal-Recessive Nonsyndromic Hearing Impairment DFNB89  Regie Lyn P. Santos-Cortez, Kwanghyuk.
Emma L. Baple, Reza Maroofian, Barry A. Chioza, Maryam Izadi, Harold E

Emma L. Baple, Reza Maroofian, Barry A. Chioza, Maryam Izadi, Harold E
A Homozygous Mutation in the Tight-Junction Protein JAM3 Causes Hemorrhagic Destruction of the Brain, Subependymal Calcification, and Congenital Cataracts 

A Homozygous Mutation in the Tight-Junction Protein JAM3 Causes Hemorrhagic Destruction of the Brain, Subependymal Calcification, and Congenital Cataracts 
Volume 117, Issue 3, Pages (September 1999)

Volume 117, Issue 3, Pages (September 1999)
Autosomal-Recessive Early-Onset Retinitis Pigmentosa Caused by a Mutation in PDE6G, the Gene Encoding the Gamma Subunit of Rod cGMP Phosphodiesterase 

Autosomal-Recessive Early-Onset Retinitis Pigmentosa Caused by a Mutation in PDE6G, the Gene Encoding the Gamma Subunit of Rod cGMP Phosphodiesterase 

Similar presentations

Ads by Google