Novel FGFR1 mutations in Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism: evidence for the involvement of an alternatively spliced.

Slides:

Advertisements

Similar presentations

A Novel Mutation in FGFR3 Causes Camptodactyly, Tall Stature, and Hearing Loss (CATSHL) Syndrome Reha M. Toydemir, Anna E. Brassington, Pınar Bayrak-Toydemir,

Advertisements

Novel homozygous nonsense mutations in the luteinizing hormone receptor (LHCGR) gene associated with 46,XY primary amenorrhea Imen Ben Hadj Hmida, Ph.D.,

Shidou Zhao, Ph. D. , Guangyu Li, M. Sc. , Raymond Dalgleish, Ph. D

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

Next generation sequencing in women affected by nonsyndromic premature ovarian failure displays new potential causative genes and mutations Dora Janeth.

P. M. Kelley, D. J. Harris, B. C. Comer, J. W. Askew, T. Fowler, S. D

Fernando Zegers-Hochschild, M.D. Fertility and Sterility

Novel mutations and polymorphisms in the CFTR gene associated with three subtypes of congenital absence of vas deferens Xiaojian Yang, M.D., Qipeng Sun,

Xiaoyun Dou, M. D. , Ting Guo, M. D. , Ph. D. , Guangyu Li, M. S

Ameli Norling, M. D. , Angelica Lindén Hirschberg, M. D. , Ph. D

A new FOXL2 gene mutation in a woman with premature ovarian failure and sporadic blepharophimosis-ptosis-epicanthus inversus syndrome Frederico José.

A novel mutation c.118delA in exon 1 of the androgen receptor gene resulting in complete androgen insensitivity syndrome within a large family Karel.

William A. Paznekas, Michael L. Cunningham, Timothy D. Howard, Bruce R

Ala 586 Asp mutation in androgen receptor disrupts transactivation function without affecting androgen binding Singh Rajender, Ph.D., Nalini J. Gupta,

Identification of a novel mutation in exon 1 of androgen receptor gene in an azoospermic patient with mild androgen insensitivity syndrome: case report.

Volume 54, Issue 3, Pages (September 1998)

Ali Sazci, Ph. D. , Nesrin Ercelen, M. D. , Emel Ergul, M. S

Volume 54, Issue 3, Pages (September 1998)

Investigation of the human stem cell factor KIT ligand gene, KITLG, in women with 46,XX spontaneous premature ovarian failure Emily S. Hui, B.A., Ekemini.

Three generations of patients with lupus erythematosus and hereditary angioedema Theresa R Pacheco, MD, William L Weston, MD, Patricia C Giclas, PhD,

The prevalence of digenic mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome Samuel D. Quaynor, M.S., Hyung-Goo.

Genome-wide copy number analysis and systematic mutation screening in 58 patients with hypogonadotropic hypogonadism Yoko Izumi, M.D., Erina Suzuki,

Inherited mutation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) in empty follicle syndrome Kemal O. Yariz, Ph.D., Tom Walsh, Ph.D.,

Methylation changes in mature sperm deoxyribonucleic acid from oligozoospermic men: assessment of genetic variants and assisted reproductive technology.

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

Identification of a Novel Mutation R42P in the Gap Junction Protein β-3 Associated with Autosomal Dominant Erythrokeratoderma Variabilis Amanda Wilgoss,

Reply of the Authors Fertility and Sterility

Gadolinium radiologic contrast is a useful alternative for hysterosalpingography in patients with iodine allergy Dorette Noorhasan, M.D., Michael J.

Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene Daniel.

Integrative DNA methylation and gene expression analysis identifies discoidin domain receptor 1 association with idiopathic nonobstructive azoospermia

HOXA10 mutations in congenital absence of uterus and vagina

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.

A Novel Point Mutation Affecting the Tyrosine Kinase Domain of the TRKA Gene in a Family with Congenital Insensitivity to Pain with Anhidrosis Shinichi.

Idiopathic hypogonadotropic hypogonadism in a mother and her monozygotic twins born after a single embryo transfer Eeva-Maria Laitinen, M.D., Johanna.

A Mutation in the Variable Repeat Region of the Aggrecan Gene (AGC1) Causes a Form of Spondyloepiphyseal Dysplasia Associated with Severe, Premature.

A novel mutation of HOXA13 in a family with hand-foot-genital syndrome and the role of polyalanine expansions in the spectrum of Müllerian fusion anomalies

Mutational analysis of androgen receptor gene in four Chinese patients with male pseudohermaphroditism Xueyan Wu, M.D., Qi Zhou, M.Sc., Jiangfeng Mao,

Identification of HESX1 mutations in Kallmann syndrome

Dominique J. Verlaan, Adrian M. Siegel, Guy A. Rouleau

Cost-effectiveness analysis comparing continuation of assisted reproductive technology with conversion to intrauterine insemination in patients with low.

Volume 58, Issue 2, Pages (August 2000)

Opitz G/BBB Syndrome in Xp22: Mutations in the MID1 Gene Cluster in the Carboxy- Terminal Domain Karin Gaudenz, Erich Roessler, Nandita Quaderi, Brunella.

Akanksha Mehta, M.D., Darius A. Paduch, M.D., Ph.D.

Ken-Ichi Egoshi, Koichiro Akakura, Takaomi Kodama, Haruo Ito

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,

Jittima Dhitavat, Leonard Dode, Natalie Leslie, Anavaj Sakuntabhai

Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene Daniel.

Volume 55, Issue 1, Pages (January 1999)

M. Kathleen Clark, Ph. D. , MaryFran R. Sowers, Ph. D

Reversal of hypogonadotropic hypogonadism with tamoxifen in a patient with hyperprolactinemia resistant to dopamine agonists José M. López, M.D., Eveline.

A novel frameshift mutation in the 5α-reductase type 2 gene in Korean sisters with male pseudohermaphroditism Sung Hoon Kim, M.D., Kun Suk Kim, M.D.,

Association study between single nucleotide polymorphisms in the VEGF gene and polycystic ovary syndrome Eung-Ji Lee, M.Sc., Bermseok Oh, Ph.D., Jong-Young.

Volume 53, Issue 5, Pages (May 1998)

Detection and identification of bacterial DNA in semen

Pregnancy outcome in infertile patients with polycystic ovary syndrome who were treated with metformin Samuel S. Thatcher, M.D., Ph.D., Elizabeth M.

Eung-Ji Lee, M. Sc. , Bermseok Oh, Ph. D. , Jong-Young Lee, Ph. D

Volume 57, Issue 1, Pages (January 2000)

Emily C. Corrigan, B. S. , Margarita J. Raygada, M. Sc. , Ph. D

Impact of subclinical hypothyroidism in women with recurrent early pregnancy loss Lia A. Bernardi, M.D., Ronald N. Cohen, M.D., Mary D. Stephenson, M.D.,

A novel homozygous FBXO43 mutation associated with male infertility and teratozoospermia in a consanguineous Chinese family Ying Ma, Ph.D., Ning Xie,

Current evaluation of amenorrhea

Genetic evaluation procedures at sperm banks in the United States

Shilin Zhang, M. D. , Tao Wang, M. D. , Jun Yang, M. D. , Zhuo Liu, M

Keith A. Hansen, M. D. , Yueyi Zhang, M. D. , Robert Colver, M. D

Identification of a New Splice Form of the EDA1 Gene Permits Detection of Nearly All X- Linked Hypohidrotic Ectodermal Dysplasia Mutations Alex W. Monreal,

Chenming Xu, Ph. D. , Bingsen Xu, M. Sc. , Hefeng Huang, M. D

Sequence variation analysis of the prolactin receptor C-terminal region in women with premature ovarian failure Anne Bachelot, M.D., Ph.D., Justine Bouilly,

A novel Arg615Ser mutation of androgen receptor DNA-binding domain in three 46,XY sisters with complete androgen insensitivity syndrome and bilateral.

Identification of novel polymorphisms in the nuclear protein genes and their relationship with human sperm protamine deficiency and severe male infertility

Maternal serum screening markers and nuchal translucency measurements in in vitro fertilization pregnancies: a systematic review Andrea Lanes, M.Sc.,

Presentation transcript:

Novel FGFR1 mutations in Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism: evidence for the involvement of an alternatively spliced isoform Catarina Gonçalves, M.Sc., Margarida Bastos, M.D., Duarte Pignatelli, M.D., Ph.D., Teresa Borges, M.D., José M. Aragüés, M.D., Fernando Fonseca, M.D., Bernardo D. Pereira, M.D., Sílvia Socorro, Ph.D., Manuel C. Lemos, M.D., Ph.D. Fertility and Sterility Volume 104, Issue 5, Pages 1261-1267.e1 (November 2015) DOI: 10.1016/j.fertnstert.2015.07.1142 Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Identification of FGFR1 mutations in affected families. (A) Pedigrees of affected families and mutation nomenclature at the nucleotide and protein level. Filled symbols represent patients with Kallmann syndrome (family 3, 5, and 6) or normosmic idiopathic hypogonadotropic hypogonadism (family 1, 2, and 4); open symbols represent unaffected individuals; open symbols with black dot represent unaffected carriers of the mutation; open symbols with question mark represent untested individuals; squares denote men; circles denote women; and oblique lines through symbols represent deceased individuals. (B) DNA sequence analysis of normal individuals (above) and patients (below). The positions of the mutations are indicated by asterisks. All patients were heterozygous for the mutated nucleotides. In the case of frameshift mutations (families 2 and 5), only the cloned mutated allele is represented. (C) Confirmation of mutations by agarose gel electrophoresis of restriction enzyme-digested fragments (BsrI, PflMI, MspI, AccI, AseI, and BstUI). Lanes correspond to family members represented in (A) and normal controls (C). Fertility and Sterility 2015 104, 1261-1267.e1DOI: (10.1016/j.fertnstert.2015.07.1142) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 1 Mapping of the S96C and M719V FGFR1 missense mutations onto the crystal structures of the FGFR1-IIIc protein. (A) The mutated S96 residue (red) is mapped on the immunoglobulin-like domain 1 (D1) solution structure (Protein Data Bank ID: 2CR3). D1 is colored in green. The S96 residue points into the hydrophobic nucleus of D1, establishing links with the hydrophobic residues (V116, L51, Y99) and contributing to the tertiary fold of this domain. (B) The mutated M719 residue (red) is mapped on the FGFR1 kinase domain (Protein Data Bank ID: 3GQI). The amino-terminal (NT) lobe is in pink. The kinase hinge region is in grey; the activation loop is in yellow; and the carboxy-terminal (CT) lobe is in green. The M719 residue maps to the loop region connecting helices αH and αG, keeping contacts with hydrophobic amino acids from helices αH and αF (M733, W691, V688, W737, M719, Y730). Fertility and Sterility 2015 104, 1261-1267.e1DOI: (10.1016/j.fertnstert.2015.07.1142) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions