Autosomal-Dominant Woolly Hair Resulting from Disruption of Keratin 74 (KRT74), a Potential Determinant of Human Hair Texture Yutaka Shimomura, Muhammad.

Slides:

Advertisements

Similar presentations

Mutation in NSUN2, which Encodes an RNA Methyltransferase, Causes Autosomal- Recessive Intellectual Disability Muzammil Ahmad Khan, Muhammad Arshad Rafiq,

Advertisements

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

Novel Functional Single Nucleotide Polymorphisms in the Latent Transforming Growth Factor-β Binding Protein-1L Promoter Tomomi Higashi, Satoru Kyo, Masaki.

Homozygous Defects in LMNA, Encoding Lamin A/C Nuclear-Envelope Proteins, Cause Autosomal Recessive Axonal Neuropathy in Human (Charcot-Marie-Tooth Disorder.

Characterization of the Human Hair Shaft Cuticle–Specific Keratin-Associated Protein 10 Family Hiroki Fujikawa, Atsushi Fujimoto, Muhammad Farooq, Masaaki.

Mutations in AGBL1 Cause Dominant Late-Onset Fuchs Corneal Dystrophy and Alter Protein-Protein Interaction with TCF4 S. Amer Riazuddin, Shivakumar Vasanth,

A Novel Mutation and Large Size Polymorphism Affecting the V2 Domain of Keratin 1 in an African-American Family with Severe, Diffuse Palmoplantar Keratoderma.

A Nonsense Mutation in the Human Homolog of Drosophila rogdi Causes Kohlschutter– Tonz Syndrome Adi Mory, Efrat Dagan, Barbara Illi, Philippe Duquesnoy,

A Mutation in the Vesicle-Trafficking Protein VAPB Causes Late-Onset Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis Agnes L. Nishimura, Miguel.

Volume 14, Issue 5, Pages (March 2004)

Mutations in the Transcription Factor Gene SOX18 Underlie Recessive and Dominant Forms of Hypotrichosis-Lymphedema-Telangiectasia Alexandre Irrthum,

A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa Goranka Tanackovic, Adriana Ransijn,

Mutations in TPRN Cause a Progressive Form of Autosomal-Recessive Nonsyndromic Hearing Loss Yun Li, Esther Pohl, Redouane Boulouiz, Margit Schraders,

A Truncating Mutation of CEP135 Causes Primary Microcephaly and Disturbed Centrosomal Function Muhammad Sajid Hussain, Shahid Mahmood Baig, Sascha Neumann,

Volume 12, Issue 7, Pages (April 2002)

Targeted High-Throughput Sequencing Identifies Mutations in atlastin-1 as a Cause of Hereditary Sensory Neuropathy Type I Christian Guelly, Peng-Peng.

Mutations in the Keratin 85 (KRT85/hHb5) Gene Underlie Pure Hair and Nail Ectodermal Dysplasia Yutaka Shimomura, Muhammad Wajid, Mazen Kurban, Nobuyuki.

TBC1D24, an ARF6-Interacting Protein, Is Mutated in Familial Infantile Myoclonic Epilepsy Antonio Falace, Fabia Filipello, Veronica La Padula, Nicola.

HKAP1.6 and hKAP1.7, Two Novel Human High Sulfur Keratin-Associated Proteins are Expressed in the Hair Follicle Cortex Yutaka Shimomura, Noriaki Aoki,

Volume 11, Issue 4, Pages (April 2003)

Hongli Liu, M. D. , Ph. D. , Xiaofei Xu, M. D. , Ph. D. , Ting Han, M

Aoi Nakano, Hajime Nakano, Sal LaForgia, Leena Pulkkinen, Jouni Uitto

Emma L. Baple, Reza Maroofian, Barry A. Chioza, Maryam Izadi, Harold E

A Novel Keratin 5 Mutation (K5V186L) in a Family with EBS-K: a Conservative Substitution Can Lead to Development of Different Disease Phenotypes Mirjana.

Sequence Analysis and Homology Modeling Suggest That Primary Congenital Glaucoma on 2p21 Results from Mutations Disrupting Either the Hinge Region or.

Efrat Avigad Laron, Emil Aamar, David Enshell-Seijffers

Autosomal-Recessive Hypophosphatemic Rickets Is Associated with an Inactivation Mutation in the ENPP1 Gene Varda Levy-Litan, Eli Hershkovitz, Luba Avizov,

A Missense Mutation within the Helix Initiation Motif of the Keratin K71 Gene Underlies Autosomal Dominant Woolly Hair/Hypotrichosis Atsushi Fujimoto,

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

Size Polymorphisms in the Human Ultrahigh Sulfur Hair Keratin-Associated Protein 4, KAP4, Gene Family Naoyuki Kariya, Yutaka Shimomura, Masaaki Ito

Peter Ianakiev, Michael W

Capillary Malformation–Arteriovenous Malformation, a New Clinical and Genetic Disorder Caused by RASA1 Mutations Iiro Eerola, Laurence M. Boon, John.

Characterization of Human Keratin-Associated Protein 1 Family Members

Splice Site and Deletion Mutations in Keratin (KRT1 and KRT10) Genes: Unusual Phenotypic Alterations in Scandinavian Patients with Epidermolytic Hyperkeratosis

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility Tailai Chen, Yuehong Bian, Xiaoman Liu, Shigang Zhao, Keliang.

A Mutation in the Fibroblast Growth Factor 14 Gene Is Associated with Autosomal Dominant Cerebral Ataxia John C. van Swieten, Esther Brusse, Bianca M.

A Rare Case of Hypohidrotic Ectodermal Dysplasia Caused by Compound Heterozygous Mutations in the EDAR Gene Yutaka Shimomura, Nobuyuki Sato, Akinori.

A Nonsense Mutation in CRYBB1 Associated with Autosomal Dominant Cataract Linked to Human Chromosome 22q Donna S. Mackay, Olivera B. Boskovska, Harry.

Mutations in the Lipase H Gene Underlie Autosomal Recessive Woolly Hair/Hypotrichosis Yutaka Shimomura, Muhammad Wajid, Lynn Petukhova, Lawrence Shapiro,

A Missense Mutation within the Helix Termination Motif of KRT25 Causes Autosomal Dominant Woolly Hair/Hypotrichosis Xia Yu, Fuyin Chen, Cheng Ni, Guolong.

Airong Li, Sonia Davila, Laszlo Furu, Qi Qian, Xin Tian, Patrick S

A Recurrent Mutation in the ARS (Component B) Gene Encoding SLURP-1 in Turkish Families with Mal de Meleda: Evidence of a Founder Effect Guofang Hu,

Characterization of the Human Hair Keratin–Associated Protein 2 (KRTAP2) Gene Family Hiroki Fujikawa, Atsushi Fujimoto, Muhammad Farooq, Masaaki Ito,

A Missense Mutation in the Zinc-Finger Domain of the Human Hairless Gene Underlies Congenital Atrichia in a Family of Irish Travellers Wasim Ahmad, Alan.

Founder Mutations in the Lipase H Gene in Families with Autosomal Recessive Woolly Hair/Hypotrichosis Yutaka Shimomura, Muhammad Wajid, Abraham Zlotogorski,

Autosomal Recessive Hypotrichosis with Woolly Hair Caused by a Mutation in the Keratin 25 Gene Expressed in Hair Follicles Nikolay V. Zernov, Mikhail.

Mutations in the DBP-Deficiency Protein HSD17B4 Cause Ovarian Dysgenesis, Hearing Loss, and Ataxia of Perrault Syndrome Sarah B. Pierce, Tom Walsh, Karen.

TBC1D24, an ARF6-Interacting Protein, Is Mutated in Familial Infantile Myoclonic Epilepsy Antonio Falace, Fabia Filipello, Veronica La Padula, Nicola.

Biallelic Mutations in PATL2 Cause Female Infertility Characterized by Oocyte Maturation Arrest Biaobang Chen, Zhihua Zhang, Xiaoxi Sun, Yanping Kuang,

Biallelic SUN5 Mutations Cause Autosomal-Recessive Acephalic Spermatozoa Syndrome Fuxi Zhu, Fengsong Wang, Xiaoyu Yang, Jingjing Zhang, Huan Wu, Zhou.

Lethal Contractural Syndrome Type 3 (LCCS3) Is Caused by a Mutation in PIP5K1C, Which Encodes PIPKIγ of the Phophatidylinsitol Pathway Ginat Narkis,

J. Fielding Hejtmancik, Xiaodong Jiao, Anren Li, Yuri V

Characterization of Human Keratin-Associated Protein 1 Family Members

X-Linked Dominant Scapuloperoneal Myopathy Is Due to a Mutation in the Gene Encoding Four-and-a-Half-LIM Protein 1 Catarina M. Quinzii, Tuan H. Vu, K.

Deleterious Mutations in the Zinc-Finger 469 Gene Cause Brittle Cornea Syndrome Almogit Abu, Moshe Frydman, Dina Marek, Eran Pras, Uri Nir, Haike Reznik-Wolf,

Compound Heterozygosity for Novel Splice Site Mutations in the BPAG2/COL17A1 Gene Underlies Generalized Atrophic Benign Epidermolysis Bullosa Leena Pulkkinen,

Penelope R Chua, G.Shirleen Roeder Cell

A Unique Point Mutation in the PMP22 Gene Is Associated with Charcot-Marie-Tooth Disease and Deafness Margaret J. Kovach, Jing-Ping Lin, Simeon Boyadjiev,

Identification of Recurrent Mutations in the ARS (Component B) Gene Encoding SLURP-1 in Two Families with Mal de Meleda Kimberley Morine Ward, Jülide.

Mutations in POLR3A and POLR3B Encoding RNA Polymerase III Subunits Cause an Autosomal-Recessive Hypomyelinating Leukoencephalopathy Hirotomo Saitsu,

Early Onset of Severe Familial Amyotrophic Lateral Sclerosis with a SOD-1 Mutation: Potential Impact of CNTF as a Candidate Modifier Gene Ralf Giess,

An Unusual Ala12Thr Polymorphism in the 1A α-Helical Segment of the Companion Layer-Specific Keratin K6hf: Evidence for a Risk Factor in the Etiology.

Exome Sequencing Identifies CCDC8 Mutations in 3-M Syndrome, Suggesting that CCDC8 Contributes in a Pathway with CUL7 and OBSL1 to Control Human Growth

A Gene for an Autosomal Dominant Scleroatrophic Syndrome Predisposing to Skin Cancer (Huriez Syndrome) Maps to Chromosome 4q23 Young-Ae Lee, Howard P.

Mutations in NEXN, a Z-Disc Gene, Are Associated with Hypertrophic Cardiomyopathy Hu Wang, Zhaohui Li, Jizheng Wang, Kai Sun, Qiqiong Cui, Lei Song, Yubao.

Akio Tanaka, Sarah Weinel, Nikoletta Nagy, Mark O'Driscoll, Joey E

Alexandre Irrthum, Marika J

Gene Augmentation and Readthrough Rescue Channelopathy in an iPSC-RPE Model of Congenital Blindness Pawan K. Shahi, Dalton Hermans, Divya Sinha, Simran.

Identification and Functional Analysis of ZIC3 Mutations in Heterotaxy and Related Congenital Heart Defects Stephanie M. Ware, Jianlan Peng, Lirong Zhu,

Genome-Edited Triple-Recessive Mutation Alters Seed Dormancy in Wheat

Presentation transcript:

Autosomal-Dominant Woolly Hair Resulting from Disruption of Keratin 74 (KRT74), a Potential Determinant of Human Hair Texture Yutaka Shimomura, Muhammad Wajid, Lynn Petukhova, Mazen Kurban, Angela M. Christiano The American Journal of Human Genetics Volume 86, Issue 4, Pages 632-638 (April 2010) DOI: 10.1016/j.ajhg.2010.02.025 Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 1 Fine Mapping of ADWH Phenotype on Chromosome 12q12-q14.1 (A–C) Clinical appearance of ADWH. (D–G) Appearance of the hair shaft in affected individuals with ADWH. The scale bar represents 100 μm. (H) Pedigree and haplotype analysis of a Pakistani family ADWH1. The linked haplotype is indicated in red. Critical recombination events are indicated by black arrowheads. The American Journal of Human Genetics 2010 86, 632-638DOI: (10.1016/j.ajhg.2010.02.025) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 2 Identification of a Mutation in the KRT74 Gene (A) Schematic representation of the candidate region harboring the ADWH gene. The candidate region and the type II keratin gene cluster are boxed in yellow and red, respectively, and localization of four IRS-specific keratin genes, KRT71–74, is shown at the bottom. (B) A heterozygous mutation c.444C > G (p.Asn148Lys) in the KRT74 gene in affected individuals from the family ADWH1. (C) Segregation analysis of the mutation c.444C > G in the KRT74 gene. PCR products of 338 bp from the mutant (Mut) allele were digested into 234 bp and 104 bp fragments with the restriction enzyme AcuI, whereas those from the wild-type (Wt) allele were not digested. Affected individuals are indicated in red and show the digested bands of 234 bp and 104 bp from the Mut allele as well as the undigested band of 338 bp from the Wt allele. MWM, molecular weight markers. C, control individual. (D) Multiple-amino-acid sequence alignment of the helix initiation motif (HIM) of human type II keratins. K74 (K6irs4) is indicated in red. The Asn residue at amino acid position 9 in the HIM, which is invariant and completely conserved among all human type II keratins, is highlighted in yellow. The American Journal of Human Genetics 2010 86, 632-638DOI: (10.1016/j.ajhg.2010.02.025) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 3 Mutant K74 Protein Disrupts Endogenous KIF Formation in PtK2 Cells, and K74 Colocalizes with LPAR6 in Huxley's Layer of Human Hair Follicles (A–C) Ectopically expressed wild-type (Wt) K74 protein forms a KIF network via heterodimerization with endogenous K18 protein. (D–F) The p.Asn148Lys mutant (Mut) K74 protein causes a collapse of the endogenous KIF network around the nucleus. (G–I) Double immunostainings with guinea pig polyclonal anti-K74 (1:2,000) (G) and rabbit polyclonal anti-P2Y5 (LPAR6; 1:200; MBL International) (H) antibodies show that both K74 and LPAR6 proteins are coexpressed in Huxley's (Hux) layer of the IRS of human hair follicles from a normal control individual (I), whereas only LPAR6 is expressed in Henle's (He) layer of the IRS (I). The right panels are merged images, and counterstaining with DAPI is shown in blue (C, F, and I). Scale bars represent 20 μm (A) and 100 μm (G). The American Journal of Human Genetics 2010 86, 632-638DOI: (10.1016/j.ajhg.2010.02.025) Copyright © 2010 The American Society of Human Genetics Terms and Conditions