IGBMC : Institut de la Génétique et de la Biologie Moléculaire et Cellulaire

• Researchers

  Christelle GOLZIO

• Post-Doctoral Fellows

  Maria Nicla LOVIGLIO

• PhD Students

  Camille BONNET

  Gaëlle HAYOT

• Engineers & Technicians

  Chantal WEBER

Translational medicine and neurogenetics

Study of copy number variants in autism spectrum disorders and their comorbidities

Autism Spectrum Disorders (ASDs) are a group of multifactorial, heterogeneous neurodevelopmental disorders characterized by deficits in communication and social interaction, and repetitive behaviors. The prevalence is ~1% worldwide with a 4:1 male to female ratio. Several co-morbidities have been associated with Autism Spectrum Disorders including intellectual disability, craniofacial malformations, head circumference defects (micro/macrocephaly), gastrointestinal problems, and heart malformations.

CNVs (e.g. deletion, duplication, insertion, inversion) represent the most frequent types of genetic lesion in both rare and common human genetic disorders. To date, close to 500 CNVs have been associated with ASD. The interpretation of these lesions is both acute and challenging. The primary focus in our laboratory is to understand how genetic variation can impact the development and homeostasis of the nervous system. To this goal, we have developed animal models and assays to study the impact of gene dosage defects on basic neurodevelopmental processes to:

• Discover genes and alleles that contribute to diseases
• Capture and validate genetic interactions (cis- and trans-modulators)
• Identify genes implicated in ASD-associated comorbidities

The laboratory employs an innovative orthogonal approach to tackle the current challenges in the field by combining in vivo modeling in the developing zebrafish and genomic tools. Ultimately, our work will contribute to the stratification of this highly heterogeneous group of disorders and will, in turn, inform diagnosis and patient care.

• Current projects

  • Functional dissection of the 16p11.2 BP2-BP3 CNV in zebrafish and mice
  • Study of the impact on brain development and function in Kctd13 knockout mice
  • Functional dissection of the 4p16.1 CNV in a syndromic form of autism
  • Determining the impact of gene dosage perturbation of CHD8, a ASD candidate, on the development of the peripheral nervous system
  • Autism Genes And Susceptibility For Gastrointestinal Defects: Functional Studies Utilizing Zebrafish Embryo As An In Vivo Model

• Collaborations

  Erica Davis (CHDM, Duke University, USA)

  Bertrand Isidor (CHU, Nantes, France)

  Nicholas Katsanis (CHDM, Duke University, USA)

  Jean Louis Mandel (IGBMC, Illkirch, France)

  Amélie Piton (IGBMC, Illkirch, France)

  Alexandre Reymond (CIG, Lausanne, Switzerland)

  Raman Sharma (Robinson Reserch Institute, University of Adelaide, Australia)

  Michael Talkowski (MGH, Broad Institute, Boston, USA)

  Binnaz Yalcin (IGBMC, Illkirch, France)

• Prizes/Awards

  • Christelle Golzio - ANR Jeunes chercheurs grant - - 2017
  • Maria Nicla Loviglio - FRM “Post-doctorat en France” Fellowship - - 2017
  • Camille Bonnet - Région Grand-Est PhD Fellowship - - 2017
  • Christelle Golzio - LabEx INRT Starting package grant - 2016 - - 2016
  • Maria Nicla Loviglio - SNSF Early Postdoc Mobility Fellowship 2016 - - 2016

• News

• Publications

  • A dominant vimentin variant causes a rare syndrome with premature aging.

    Cogné B(1)(2), Bouameur JE(3), Hayot G(4)(5)(6)(7), Latypova X(1)(2), Pattabiraman S(8), Caillaud A(2), Si-Tayeb K(2), Besnard T(1)(2), Küry S(1)(2), Chariau C(9), Gaignerie A(9), David L(9)(10), Bordure P(11), Kaganovich D(8)(12), Bézieau S(1)(2), Golzio C(13)(14)(15)(16), Magin TM(17), Isidor B(18)(19).

    Eur J Hum Genet Feb. 17, 2020 .

  • Kctd13-deficient mice display short-term memory impairment and sex-dependent genetic interactions.

    Arbogast T(1), Razaz P(2), Ellegood J(3), McKinstry S(1), Erdin S(2), Currall B(2), Aneichyk T(2), Lerch JP(3), Qiu LR(3), Rodriguiz RM(4), Mark Henkelman R(3), Talkowski ME(2), Wetsel WC(4)(5), Golzio C(6), Katsanis N(1).

    Hum Mol Genet May 1, 2019 ; 28:1474-1486 .

  • Loss of zebrafish Ataxin-7, a SAGA subunit responsible for SCA7 retinopathy, causes ocular coloboma and malformation of photoreceptors.

    Carrillo-Rosas S(1)(2)(3)(4), Weber C(1)(2)(3)(4), Fievet L(1)(2)(3)(4), Messaddeq N(1)(2)(3)(4), Karam A(1)(2)(3)(4), Trottier Y(1)(2)(3)(4).

    Hum Mol Genet March 15, 2019 ; 28:912-927 .

  • Pathogenic variants in E3 ubiquitin ligase RLIM/RNF12 lead to a syndromic X-linked intellectual disability and behavior disorder.

    Frints SGM(1)(2), Ozanturk A(3), Rodriguez Criado G(4), Grasshoff U(5), de Hoon B(6)(7), Field M(8), Manouvrier-Hanu S(9)(10), E Hickey S(11)(12), Kammoun M(13), Gripp KW(14), Bauer C(5), Schroeder C(5), Toutain A(15)(16), Mihalic Mosher T(11)(12)(17), Kelly BJ(17), White P(12)(17), Dufke A(5), Rentmeester E(6), Moon S(3), Koboldt DC(12)(17), van Roozendaal KEP(18)(19), Hu H(20), Haas SA(21), Ropers HH(20), Murray L(8), Haan E(22)(23), Shaw M(22), Carroll R(22), Friend K(24), Liebelt J(23), Hobson L(24), De Rademaeker M(25), Geraedts J(18)(19), Fryns JP(13), Vermeesch J(13), Raynaud M(15)(16), Riess O(5), Gribnau J(6), Katsanis N(3), Devriendt K(13), Bauer P(5), Gecz J(22)(26), Golzio C(3)(27), Gontan C(6), Kalscheuer VM(28).

    Mol Psychiatry Feb 2018 ; Published online:1-22 .

  • Health-Related Quality of Life Is Severely Affected in Primary Orthostatic Tremor.

    Maugest L(1), McGovern EM(2)(3), Mazalovic K(4), Doulazmi M(5), Apartis E(6), Anheim M(7)(8)(9), Bourdain F(10), Benchetrit E(11), Czernecki V(11), Broussolle E(12)(13), Bonnet C(11), Falissard B(14), Jahanshahi M(15), Vidailhet M(11)(16), Roze E(11)(16).

    Front Neurol Jan. 15, 2018 ; 8:747 .

  • The Immune Signaling Adaptor LAT Contributes to the Neuroanatomical Phenotype of 16p11.2 BP2-BP3 CNVs.

    Loviglio MN(1), Arbogast T(2), Jnch AE(3), Collins SC(4), Popadin K(5), Bonnet CS(2), Giannuzzi G(1), Maillard AM(3), Jacquemont S(3); 16p11.2 Consortium, Yalcin B(6), Katsanis N(2), Golzio C(7), Reymond A(8).

    Am J Hum Genet Oct. 5, 2017 ; 101:564-577 .

  • Partial uniparental isodisomy of chromosome 16 unmasks a deleterious biallelic mutation in IFT140 that causes Mainzer-Saldino syndrome.

    Helm BM(1)(2), Willer JR(3), Sadeghpour A(3), Golzio C(3)(4), Crouch E(5), Vergano SS(1)(6), Katsanis N(7), Davis EE(8).

    Hum Genomics July 19, 2017 ; 11:16 .

  • De Novo Disruption of the Proteasome Regulatory Subunit PSMD12 Causes a Syndromic Neurodevelopmental Disorder.

    Kury S, Besnard T, Ebstein F, Khan TN, Gambin T, Douglas J, Bacino CA, Craigen WJ, Sanders SJ, Lehmann A, Latypova X, Khan K, Pacault M, Sacharow S, Glaser K, Bieth E, Perrin-Sabourin L, Jacquemont ML, Cho MT, Roeder E, Denomme-Pichon AS, Monaghan KG, Yuan B, Xia F, Simon S, Bonneau D, Parent P, Gilbert-Dussardier B, Odent S, Toutain A, Pasquier L, Barbouth D, Shaw CA, Patel A, Smith JL, Bi W, Schmitt S, Deb W, Nizon M, Mercier S, Vincent M, Rooryck C, Malan V, Briceno I, Gomez A, Nugent KM, Gibson JB, Cogne B, Lupski JR, Stessman HA, Eichler EE, Retterer K, Yang Y, Redon R, Katsanis N, Rosenfeld JA, Kloetzel PM, Golzio C, Bezieau S, Stankiewicz P, Isidor B.

    Am J Hum Genet April 6, 2017 ; 100:689 .

  • A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family.

    Okutman O(1)(2)(3), Muller J(4)(5), Skory V(1), Garnier JM(6), Gaucherot A(7), Baert Y(8), Lamour V(9), Serdarogullari M(10), Gultomruk M(10), Ropke A(11), Kliesch S(12), Herbepin V(13), Aknin I(14), Benkhalifa M(15), Teletin M(1), Bakircioglu E(16), Goossens E(8), Charlet-Berguerand N(7), Bahceci M(10), Tuttelmann F(11), Viville S(17)(18)(19)(20).

    J Assist Reprod Genet May 2017 ; 34:683-694 .

  • A Potential Contributory Role for Ciliary Dysfunction in the 16p11.2 600 kb BP4-BP5 Pathology.

    Migliavacca E(1), Golzio C(2), Männik K(3), Blumenthal I(4), Oh EC(2), Harewood L(5), Kosmicki JA(6), Loviglio MN(5), Giannuzzi G(5), Hippolyte L(7), Maillard AM(7), Alfaiz AA(1); 16p11.2 European Consortium, van Haelst MM(8), Andrieux J(9), Gusella JF(10), Daly MJ(6), Beckmann JS(11), Jacquemont S(7), Talkowski ME(10), Katsanis N(12), Reymond A(13).

    Am J Hum Genet May 7, 2015 ; 96:784-96 .

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