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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2014

Open Access 01-12-2014 | Research

CNS involvement in OFD1 syndrome: a clinical, molecular, and neuroimaging study

Authors: Ennio Del Giudice, Marina Macca, Floriana Imperati, Alessandra D’Amico, Philippe Parent, Laurent Pasquier, Valerie Layet, Stanislas Lyonnet, Veronique Stamboul-Darmency, Christel Thauvin-Robinet, Brunella Franco, Oral-Facial-Digital Type I (OFD1) Collaborative Group

Published in: Orphanet Journal of Rare Diseases | Issue 1/2014

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Abstract

Background

Oral-facial-digital type 1 syndrome (OFD1; OMIM 311200) belongs to the expanding group of disorders ascribed to ciliary dysfunction. With the aim of contributing to the understanding of the role of primary cilia in the central nervous system (CNS), we performed a thorough characterization of CNS involvement observed in this disorder.

Methods

A cohort of 117 molecularly diagnosed OFD type I patients was screened for the presence of neurological symptoms and/or cognitive/behavioral abnormalities on the basis of the available information supplied by the collaborating clinicians. Seventy-one cases showing CNS involvement were further investigated through neuroimaging studies and neuropsychological testing.

Results

Seventeen patients were molecularly diagnosed in the course of this study and five of these represent new mutations never reported before. Among patients displaying neurological symptoms and/or cognitive/behavioral abnormalities, we identified brain structural anomalies in 88.7%, cognitive impairment in 68%, and associated neurological disorders and signs in 53% of cases. The most frequently observed brain structural anomalies included agenesis of the corpus callosum and neuronal migration/organisation disorders as well as intracerebral cysts, porencephaly and cerebellar malformations.

Conclusions

Our results support recent published findings indicating that CNS involvement in this condition is found in more than 60% of cases. Our findings correlate well with the kind of brain developmental anomalies described in other ciliopathies. Interestingly, we also described specific neuropsychological aspects such as reduced ability in processing verbal information, slow thought process, difficulties in attention and concentration, and notably, long-term memory deficits which may indicate a specific role of OFD1 and/or primary cilia in higher brain functions.
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Literature
1.
Hildebrandt F, Benzing T, Katsanis N: Ciliopathies. N Eng J Med. 2011, 364: 1533-1543. 10.1056/NEJMra1010172.CrossRef
2.
3.
Papillon-Leage M, Psaume J: Une malformation hereditaire de la muquese buccale: brides et freins anomaux. Rev Stomatol. 1954, 55: 209-227.
4.
Gurrieri F, Franco B, Toriello H, Neri G: Oral -facial-digital syndromes: a review and diagnostic guidelines. Am J Med Genet. 2007, 143A: 3314-3323. 10.1002/ajmg.a.32032.CrossRefPubMed
5.
Macca M, Franco B: The molecular basis of oral-facial-digital syndrome, type 1. Am J Med Genet C Semin Med Genet. 2009, 151C: 318-325. 10.1002/ajmg.c.30224.CrossRefPubMed
6.
Franco B, Ballabio A: X-inactivation and human disease: X-linked dominant male-lethal disorders. Curr Opin Genet Dev. 2006, 16: 254-259. 10.1016/j.gde.2006.04.012.CrossRefPubMed
7.
Thauvin-Robinet C, Cossee M, Cormier-Daire V, Van Maldergem L, Toutain A, Alembik Y, Bieth E, Layet V, Parent P, David A, Goldenberg A, Mortier G, Héron D, Sagot P, Bouvier AM, Huet F, Cusin V, Donzel A, Devys D, Teyssier JR, Faivre L: Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: a French and Belgian collaborative study. J Med Genet. 2006, 43: 54-61. 10.1136/jmg.2006.042440.CrossRefPubMedPubMedCentral
8.
Prattichizzo C, Macca M, Novelli V, Giorgio G, Barra A, Franco B: Mutational spectrum of the oral-facial-digital type I syndrome: a study on a large collection of patients. Hum Mutat. 2008, 29: 1237-1246. 10.1002/humu.20792.CrossRefPubMed
9.
Bisschoff IJ, Zeschnigk C, Horn D, Wellek B, Riess A, Wessels M, Willems P, Jensen P, Busche A, Bekkebraten J, Chopra M, Hove HD, Evers C, Heimdal K, Kaiser AS, Kunstmann E, Robinson KL, Linné M, Martin P, McGrath J, Pradel W, Prescott KE, Roesler B, Rudolf G, Siebers-Renelt U, Tyshchenko N, Wieczorek D, Wolff G, Dobyns WB, Morris-Rosendahl DJ: Novel mutations including deletions of the entire OFD1 gene in 30 families with type 1 orofaciodigital syndrome: a study of the extensive clinical variability. Hum Mutat. 2013, 34: 237-247. 10.1002/humu.22224.CrossRefPubMed
10.
de Conciliis L, Marchitiello A, Wapenaar MC, Borsani G, Giglio S, Mariani M, Consalez GG, Zuffardi O, Franco B, Ballabio A, Banfi S: Characterization of Cxorf5 (71-7A), a novel human cDNA mapping to Xp22 and encoding a protein containing coiled-coil a-helical domains. Genomics. 1998, 51: 243-250. 10.1006/geno.1998.5348.CrossRefPubMed
11.
Ferrante MI, Giorgio G, Feather SA, Bulfone A, Wright V, Ghiani M, Selicorni A, Gammaro L, Scolari F, Woolf AS, Sylvie O, Bernard L, Malcolm S, Winter R, Ballabio A, Franco B: Identification of the gene for oral-facial-digital type I syndrome. Am J Hum Genet. 2001, 68: 569-576. 10.1086/318802.CrossRefPubMedPubMedCentral
12.
Budny B, Chen W, Omran H, Fliegauf M, Tzschach A, Wisniewska M, Jensen LR, Raynaud M, Shoichet SA, Badura M, Lenzner S, Latos-Bielenska A, Ropers HH: A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. Hum Genet. 2006, 120: 171-178. 10.1007/s00439-006-0210-5.CrossRefPubMed
13.
Coene KL, Roepman R, Doherty D, Afroze B, Kroes HY, Letteboer SJ, Ngu LH, Budny B, van Wijk E, Gorden NT, Azhimi M, Thauvin-Robinet C, Veltman JA, Boink M, Kleefstra T, Cremers FP, van Bokhoven H, de Brouwer AP: OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5-encoded lebercilin. Am J Hum Genet. 2009, 85: 465-481. 10.1016/j.ajhg.2009.09.002.CrossRefPubMedPubMedCentral
14.
Field M, Scheffer IE, Gill D, Wilson M, Christie L, Shaw M, Gardner A, Glubb G, Hobson L, Corbett M, Friend K, Willis-Owen S, Gecz J: Expanding the molecular basis and phenotypic spectrum of X-linked Joubert syndrome associated with OFD1 mutations. Eur J Hum Genet. 2012, 20: 806-809. 10.1038/ejhg.2012.9.CrossRefPubMedPubMedCentral
15.
Juric-Sekhar G, Adkins J, Doherty D, Hevner RF: Joubert syndrome: brain and spinal cord malformations in genotyped cases and implications for neurodevelopmental functions of primary cilia. Acta Neuropathol. 2012, 123: 695-709. 10.1007/s00401-012-0951-2.CrossRefPubMed
16.
Thauvin-Robinet C, Thomas S, Sinico M, Aral B, Burglen L, Gigot N, Dollfus H, Rossignol S, Raynaud M, Philippe C, Badens C, Touraine R, Gomes C, Franco B, Lopez E, Elkhartoufi N, Faivre L, Munnich A, Boddaert N, Van Maldergem L, Encha-Razavi F, Lyonnet S, Vekemans M, Escudier E, Attié-Bitach T: OFD1 mutations in males: phenotypic spectrum and ciliary basal body docking impairment. Clin Genet. 2013, 84: 86-90. 10.1111/cge.12013.CrossRefPubMed
17.
Webb TR, Parfitt DA, Gardner JC, Martinez A, Bevilacqua D, Davidson AE, Zito I, Thiselton DL, Ressa JH, Apergi M, Schwarz N, Kanuga N, Michaelides M, Cheetham ME, Gorin MB, Hardcastle AJ: Deep intronic mutation in OFD1, identified by targeted genomic next-generation sequencing, causes a severe form of X-linked retinitis pigmentosa (RP23). Hum Mol Genet. 2012, 21: 3647-3654. 10.1093/hmg/dds194.CrossRefPubMedPubMedCentral
18.
Romio L, Wright V, Price K, Winyard PJ, Donnai D, Porteous ME, Franco B, Giorgio G, Malcolm S, Woolf AS, Feather SA: OFD1, the gene mutated in Oral-Facial-Digital Syndrome Type 1, is expressed in the metanephros and in human embryonic renal mesenchymal cells. J Am Soc Nephrol. 2003, 14: 680-689. 10.1097/01.ASN.0000054497.48394.D2.CrossRefPubMed
19.
Giorgio G, Alfieri M, Prattichizzo C, Zullo A, Cairo S, Franco B: Functional characterization of the OFD1 protein reveals a nuclear localization and physical interaction with subunits of a chromatin remodeling complex. Mol Biol Cell. 2007, 18: 4397-4404. 10.1091/mbc.E07-03-0198.CrossRefPubMedPubMedCentral
20.
Ferrante MI, Zullo A, Barra A, Bimonte S, Messaddeq N, Studer M, Dolle P, Franco B: Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification. Nat Genet. 2006, 38: 112-117. 10.1038/ng1684.CrossRefPubMed
21.
Corbit KC, Shyer AE, Dowdle WE, Gaulden J, Singla V, Chen MH, Chuang PT, Reiter JF: Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms. Nat Cell Biol. 2008, 10: 70-76. 10.1038/ncb1670.CrossRefPubMed
22.
Singla V, Romaguera-Ros M, Garcia-Verdugo JM, Reiter JF: Ofd1, a human disease gene, regulates the length and distal structure of centrioles. Dev Cell. 2010, 18: 410-424. 10.1016/j.devcel.2009.12.022.CrossRefPubMedPubMedCentral
23.
Wood BP, Young LW, Townes PL: Cerebral abnormalities in the oral-facial-digital syndrome. Pediatr Radiol. 1975, 3: 130-136. 10.1007/BF01006897.CrossRefPubMed
24.
Towfighi J, Berlin CM jr, Ladda RL, Frauenhoffer EE, Lehman RA: Neuropathology of oral-facial-digital syndromes. Arch Pathol Lab Med. 1985, 109: 642-646.PubMed
25.
Odent S, Le Marec B, Toutain A, David A, Vigneron J, Treguier C, Jouan H, Millon J, Fryns J-P, Verloes A: Central nervous system malformations and early end-stage renal disease in Oro-facio-digital syndrome type 1: A review. Am J Med Genet. 1998, 75: 389-394. 10.1002/(SICI)1096-8628(19980203)75:4<389::AID-AJMG8>3.0.CO;2-L.CrossRefPubMed
26.
Holub M, Potocki L, Bodamer OA: Central nervous system malformations in oral-facial-digital syndrome, type 1. Am J Med Genet A. 2005, 136: 218.CrossRefPubMed
27.
D’Angelo A, De Angelis A, Avallone B, Piscopo I, Tammaro R, Studer M, Franco B: Ofd1 controls Dorso-Ventral patterning and axoneme elongation during embryonic brain development. PLoS One. 2012, 7: e52937-10.1371/journal.pone.0052937.CrossRefPubMedPubMedCentral
28.
Thauvin-Robinet C, Franco B, Saugier-Veber P, Aral B, Gigot N, Donzel A, Van Maldergem L, Bieth E, Layet V, Mathieu M, Teebi A, Lespinasse J, Callier P, Mugneret F, Masurel-Paulet A, Gautier E, Huet F, Teyssier JR, Tosi M, Frébourg T, Faivre L: Genomic deletions of OFD1 account for 23% of oral-facial-digital type 1 syndrome after negative DNA sequencing. Hum Mutat. 2009, 30: E320-E329. 10.1002/humu.20888.CrossRefPubMed
29.
Wildeman M, van Ophuizen E, den Dunnen JT, Taschner PE: Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker. Hum Mutat. 2008, 29: 6-13. 10.1002/humu.20654.CrossRefPubMed
30.
Wechsler D: Wechsler Intelligence Scale for Children-Third Edition (WISC III). 1991, San Antonio (TX): The Psychological Corporation
31.
American Psychiatric Association: DSM-IV-TR Diagnostic and Statistic Manual of Mental Disorders, Text Revision.DSM-IVth edition. Washington, DC: APA, 2000.
32.
Beery KE: Manual for the Developmental Test of Visual-Motor Integration (VMI). 1989, Cleveland, Ohio: Modern Curriculum Press, 3 revision
33.
Reynolds C, Bigler E: Test of Memory and Learning: Examiner’s Manual. 1994, Austin, TX: PRO-ED
34.
Rey A: L’examen psychologique dans les cas d’encephalopathie traumatique. Archives de Psychologie. 1941, 28: 215-285.
35.
Osterrieth PA: Filetest de copie d’une figure complex: contribution a l’etude de la perception et de la memoire. Archives de Psychologie. 1944, 30: 286.
36.
Axia G: Test del Primo Linguaggio (TPL). 1995, Firenze, Italy: Organizzazioni Speciali
37.
Cianchetti C, Fancello S: Test di Valutazione del Linguaggio. 1997, Trento, Italy: Erickson
38.
Ferrari E, De Renzi E, Faglioni P, Barbieri E: Standardizzazione di una batteria per la valutazione dei disturbi del linguaggio in età scolare. Neuropsich Infant. 1981, 235–236: 145-158.
39.
Heaton RK, Chelune GJ, Talley JL, Kay GG, Curtiss G: The Wisconsin Card Sorting Test (WCST). 1993, Odessa, FL: Psychological Assessment Resources
40.
Achenbach TM, Rescorla L: Manual for the Child Behavior Checklist (CBCL). 2000, Burlington, VT: University of Vermont Department of Psychiatry
41.
Saal S, Faivre L, Aral B, Gigot N, Toutain A, Van Maldergem L, Destree A, Maystadt I, Cosyns JP, Jouk PS, Loeys B, Chauveau D, Bieth E, Layet V, Mathieu M, Lespinasse J, Teebi A, Franco B, Gautier E, Binquet C, Masurel-Paulet A, Mousson C, Gouyon JB, Huet F, Thauvin-Robinet C: Renal insufficiency, a frequent complication with age in oral-facial-digital syndrome type I. Clin Genet. 2010, 77: 258-265. 10.1111/j.1399-0004.2009.01290.x.CrossRefPubMed
42.
Liu JS: Molecular genetics of neuronal migration disorders. Curr Neurol Neurosci Rep. 2011, 11: 171-178. 10.1007/s11910-010-0176-5.CrossRefPubMed
43.
Steinlin M: Cerebellar disorders in childhood: cognitive problems. Cerebellum. 2008, 7: 607-610. 10.1007/s12311-008-0083-3.CrossRefPubMed
44.
Poretti A, Huisman TA, Scheer I, Boltshauser E: Joubert syndrome and related disorders: spectrum of neuroimaging findings in 75 patients. Am J Neuroradiol. 2011, 32: 1459-1463. 10.3174/ajnr.A2517.CrossRefPubMed
45.
46.
Poretti A, Vitiello G, Hennekam RC, Arrigoni F, Bertini E, Borgatti R, Brancati F, D’Arrigo S, Faravelli F, Giordano L, Huisman TA, Iannicelli M, Kluger G, Kyllerman M, Landgren M, Lees MM, Pinelli L, Romaniello R, Scheer I, Schwarz CE, Spiegel R, Tibussek D, Valente EM, Boltshauser E: Delineation and diagnostic criteria of Oral-Facial-Digital Syndrome type VI. Orphanet J Rare Dis. 2012, 7: 4-10.1186/1750-1172-7-4.CrossRefPubMedPubMedCentral
47.
Sattar S, Gleeson JG: The ciliopathies in neuronal development: a clinical approach to investigation of Joubert syndrome and Joubert syndrome-related disorders. Dev Med Child Neurol. 2011, 53: 793-798. 10.1111/j.1469-8749.2011.04021.x.CrossRefPubMedPubMedCentral
48.
Darmency-Stamboul V, Burglen L, Lopez E, Mejean N, Dean J, Franco B, Rodriguez D, Lacombe D, Desguerres I, Cormier-Daire V, Doray B, Pasquier L, Gonzales M, Pastore M, Crenshaw ML, Huet F, Gigot N, Aral B, Callier P, Faivre L, Attié-Bitach T, Thauvin-Robinet C: Detailed clinical, genetic and neuroimaging characterization of OFD VI syndrome. Eur J Med Genet. 2013, 56: 301-308. 10.1016/j.ejmg.2013.03.004.CrossRefPubMed
49.
Lopez E, Thauvin-Robinet C, Reversade B, Khartoufi NE, Devisme L, Holder M, Ansart-Franquet H, Avila M, Lacombe D, Kleinfinger P, Kaori I, Takanashi J, Le Merrer M, Martinovic J, Noël C, Shboul M, Ho L, Güven Y, Razavi F, Burglen L, Gigot N, Darmency-Stamboul V, Thevenon J, Aral B, Kayserili H, Huet F, Lyonnet S, Le Caignec C, Franco B, Rivière JB: C5orf42 is the major gene responsible for OFD syndrome type VI. Hum Genet. 2014, 133: 367-377. 10.1007/s00439-013-1385-1.CrossRefPubMed
50.
Paetau A, Salonen R, Haltia M: Brain pathology in the Meckel syndrome: a study of 59 cases. Clin Neuropathol. 1985, 4: 56-62.PubMed
51.
Keppler-Noreuil KM, Blumhorst C, Sapp JC, Brinckman D, Johnston J, Nopoulos PC, Biesecker LG: Brain tissue- and region-specific abnormalities on volumetric MRI scans in 21 patients with Bardet-Biedl syndrome (BBS). BMC Med Genet. 2011, 12: 101.CrossRefPubMedPubMedCentral
52.
Brinckman DD, Keppler-Noreuil KM, Blumhorst C, Biesecker LG, Sapp JC, Johnston JJ, Wiggs EA: Cognitive, sensory, and psychosocial characteristics in patients with Bardet-Biedl syndrome. Am J Med Genet Part A. 2013, 161A: 2964-2971.CrossRefPubMed
53.
54.
Neugebauer JM, Amack JD, Peterson AG, Bisgrove BW, Yost HJ: FGF signalling during embryo development regulates cilia length in diverse epithelia. Nature. 2009, 458: 651-654. 10.1038/nature07753.CrossRefPubMedPubMedCentral
55.
Vaughan S, Dawe HR: Common themes in centriole and centrosome movements. Trends Cell Biol. 2011, 21: 57-66. 10.1016/j.tcb.2010.09.004.CrossRefPubMed
56.
Higginbotham H, Eom TY, Mariani LE, Bachleda A, Hirt J, Gukassyan V, Cusack CL, Lai C, Caspary T, Anton ES: Arl13b in primary cilia regulates the migration and placement of interneurons in the developing cerebral cortex. Dev Cell. 2012, 23: 925-938. 10.1016/j.devcel.2012.09.019.CrossRefPubMedPubMedCentral
57.
Higginbotham H, Guo J, Yokota Y, Umberger NL, Su CY, Li J, Verma N, Hirt J, Ghukasyan V, Caspary T, Anton ES: Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation. Nat Neurosci. 2013, 16: 1000-1007. 10.1038/nn.3451.CrossRefPubMedPubMedCentral
58.
Hunkapiller J, Singla V, Seol A, Reiter JF: The ciliogenic protein Oral-Facial-Digital 1 regulates the neuronal differentiation of embryonic stem cells. Stem Cells Dev. 2011, 20: 831-841. 10.1089/scd.2010.0362.CrossRefPubMedPubMedCentral
59.
Breunig JJ, Sarkisian MR, Arellano JI, Morozov YM, Ayoub AE, Sojitra S, Wang B, Flavell RA, Rakic P, Town T: Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog signaling. Proc Natl Acad Sci U S A. 2008, 105: 13127-13132. 10.1073/pnas.0804558105.CrossRefPubMedPubMedCentral
60.
Bennouna-Greene V, Kremer S, Stoetzel C, Christmann D, Schuster C, Durand M, Verloes A, Sigaudy S, Holder-Espinasse M, Godet J, Brandt C, Marion V, Danion A, Dietemann JL, Dollfus H: Hippocampal dysgenesis and variable neuropsychiatric phenotypes in patients with Bardet-Biedl syndrome underline complex CNS impact of primary cilia. Clin Genet. 2011, 80: 523-531. 10.1111/j.1399-0004.2011.01688.x.CrossRefPubMed
61.
Poretti A, Dietrich Alber F, Brancati F, Dallapiccola B, Valente EM, Boltshauser E: Normal cognitive functions in joubert syndrome. Neuropediatrics. 2009, 40: 287-290. 10.1055/s-0030-1249630.CrossRefPubMed
62.
Whitfield JF, Chakravarthy BR: The neuronal primary cilium: driver of neurogenesis and memory formation in the hippocampal dentate gyrus?. Cell Signal. 2009, 21: 1351-1355. 10.1016/j.cellsig.2009.02.013.CrossRefPubMed
63.
Deng W, Aimone JB, Gage FH: New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?. Nat Rev Neurosci. 2010, 11: 339-350. 10.1038/nrn2822.CrossRefPubMedPubMedCentral
64.
Einstein EB, Patterson CA, Hon BJ, Regan KA, Reddi J, Melnikoff DE, Mateer MJ, Schulz S, Johnson BN, Tallent MK: Somatostatin signaling in neuronal cilia is critical for object recognition memory. J Neurosci. 2010, 30: 4306-4314. 10.1523/JNEUROSCI.5295-09.2010.CrossRefPubMedPubMedCentral
65.
Stanic D, Malmgren H, He H, Scott L, Aperia A, Hokfelt T: Developmental changes in frequency of the ciliary somatostatin receptor 3 protein. Brain Res. 2009, 1249: 101-112.CrossRefPubMed
Metadata
Title
CNS involvement in OFD1 syndrome: a clinical, molecular, and neuroimaging study
Authors
Ennio Del Giudice
Marina Macca
Floriana Imperati
Alessandra D’Amico
Philippe Parent
Laurent Pasquier
Valerie Layet
Stanislas Lyonnet
Veronique Stamboul-Darmency
Christel Thauvin-Robinet
Brunella Franco
Oral-Facial-Digital Type I (OFD1) Collaborative Group
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2014
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-9-74

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