Homozygous deletion of a gene-free region of 4p15 in a child with multiple anomalies: Could biallelic loss of conserved, non-coding elements lead to a phenotype?

European Journal of Medical Genetics

Volumn 55, Issue 1, 2012, Pages 63-66

  Makrythanasis, Periklis ^a   Gimelli, Stefania ^b   Béna, Frédérique ^b   Dahoun, Sophie ^b   Morris, Michael A ^b   Antonarakis, Stylianos E ^a,b   Bottani, Armand ^b  

^a UNIVERSITY OF GENEVA MEDICAL SCHOOL   (Switzerland)

^b GENEVA UNIVERSITY HOSPITALS   (Switzerland)

Author keywords

Chr 4p15.1; Cognitive impairment; Consanguinity; Deafness; Homozygous deletion; Mild dysmorphism; Postaxial polydactyly

Indexed keywords

ALLELE; ARTICLE; AUTISM; CASE REPORT; CHILD; CHROMOSOME 4P; CHROMOSOME DELETION 4; COGNITIVE DEFECT; CONSANGUINEOUS MARRIAGE; DISEASE ASSOCIATION; DISEASE SEVERITY; FACE DYSMORPHIA; GENETIC ASSOCIATION; GENETIC CONSERVATION; HEARING IMPAIRMENT; HOMOZYGOSITY; HUMAN; MALE; PHENOTYPE; POLYDACTYLY;

ABNORMALITIES, MULTIPLE; ALLELES; AUTISTIC DISORDER; BASE SEQUENCE; CHILD, PRESCHOOL; CHROMOSOME DELETION; CHROMOSOMES, HUMAN, PAIR 4; COGNITION DISORDERS; COMPARATIVE GENOMIC HYBRIDIZATION; CONSANGUINITY; CONSERVED SEQUENCE; DEAFNESS; HOMOZYGOTE; HUMANS; MALE; PHENOTYPE; POLYDACTYLY;

EID: 84857191062     PISSN: 17697212     EISSN: 18780849     Source Type: Journal    
DOI: 10.1016/j.ejmg.2011.11.001     Document Type: Article

References (21)

1. Ahituv N., Zhu Y., Visel A., Holt A., Afzal V., Pennacchio L.A., Rubin E.M. Deletion of ultraconserved elements yields viable mice. PLoS Biol. 2007, 5. e234.
2. Beckmann J.S., Estivill X., Antonarakis S.E. Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability. Nat. Rev. Genet. 2007, 8:639-646.
3. Chouery E., Pangrazio A., Frattini A., Villa A., Van Wesenbeeck L., Piters E., Van Hul W., Coxon F.P., Schouten T., Helfrich M., Lefranc G., Megarbane A. A new familial sclerosing bone dysplasia. J. Bone Miner. Res. 2010, 25:676-680.
4. Curry C.J., Mao R., Aston E., Mongia S.K., Treisman T., Procter M., Chou B., Whitby H., South S.T., Brothman A.R. Homozygous deletions of a copy number change detected by array CGH: a new cause for mental retardation?. Am. J. Med. Genet. A 2008, 146A:1903-1910.
5. Ghahramani Seno M.M., Kwan B.Y., Lee-Ng K.K., Moessner R., Lionel A.C., Marshall C.R., Scherer S.W. Human PTCHD3 nulls: rare copy number and sequence variants suggest a non-essential gene. BMC Med. Genet. 2011, 12:45.
6. Kalay E., Yigit G., Aslan Y., Brown K.E., Pohl E., Bicknell L.S., Kayserili H., Li Y., Tuysuz B., Nurnberg G., Kiess W., Koegl M., Baessmann I., Buruk K., Toraman B., Kayipmaz S., Kul S., Ikbal M., Turner D.J., Taylor M.S., Aerts J., Scott C., Milstein K., Dollfus H., Wieczorek D., Brunner H.G., Hurles M., Jackson A.P., Rauch A., Nurnberg P., Karaguzel A., Wollnik B. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat. Genet. 2011, 43:23-26.
7. Khan M.A., Rafiq M.A., Noor A., Ali N., Ali G., Vincent J.B., Ansar M. A novel deletion mutation in the TUSC3 gene in a consanguineous Pakistani family with autosomal recessive nonsyndromic intellectual disability. BMC Med. Genet. 2011, 12:56.
8. Knijnenburg J., Oberstein S.A., Frei K., Lucas T., Gijsbers A.C., Ruivenkamp C.A., Tanke H.J., Szuhai K. A homozygous deletion of a normal variation locus in a patient with hearing loss from non-consanguineous parents. J. Med. Genet. 2009, 46:412-417.
9. Koifman A., Feigenbaum A., Bi W., Shaffer L.G., Rosenfeld J., Blaser S., Chitayat D. A homozygous deletion of 8q24.3 including the NIBP gene associated with severe developmental delay, dysgenesis of the corpus callosum, and dysmorphic facial features. Am. J. Med. Genet. A 2010, 152A:1268-1272.
10. Koolen D.A., Sharp A.J., Hurst J.A., Firth H.V., Knight S.J., Goldenberg A., Saugier-Veber P., Pfundt R., Vissers L.E., Destree A., Grisart B., Rooms L., Van der Aa N., Field M., Hackett A., Bell K., Nowaczyk M.J., Mancini G.M., Poddighe P.J., Schwartz C.E., Rossi E., De Gregori M., Antonacci-Fulton L.L., McLellan M.D., Garrett J.M., Wiechert M.A., Miner T.L., Crosby S., Ciccone R., Willatt L., Rauch A., Zenker M., Aradhya S., Manning M.A., Strom T.M., Wagenstaller J., Krepischi-Santos A.C., Vianna-Morgante A.M., Rosenberg C., Price S.M., Stewart H., Shaw-Smith C., Brunner H.G., Wilkie A.O., Veltman J.A., Zuffardi O., Eichler E.E., de Vries B.B. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. J. Med. Genet. 2008, 45:710-720.
11. Lander E.S., Botstein D. Mapping complex genetic traits in humans: new methods using a complete RFLP linkage map. Cold Spring Harb. Symp. Quant. Biol. 1986, 51(Pt 1):49-62.
12. Mefford H.C., Sharp A.J., Baker C., Itsara A., Jiang Z., Buysse K., Huang S., Maloney V.K., Crolla J.A., Baralle D., Collins A., Mercer C., Norga K., de Ravel T., Devriendt K., Bongers E.M., de Leeuw N., Reardon W., Gimelli S., Bena F., Hennekam R.C., Male A., Gaunt L., Clayton-Smith J., Simonic I., Park S.M., Mehta S.G., Nik-Zainal S., Woods C.G., Firth H.V., Parkin G., Fichera M., Reitano S., Lo Giudice M., Li K.E., Casuga I., Broomer A., Conrad B., Schwerzmann M., Raber L., Gallati S., Striano P., Coppola A., Tolmie J.L., Tobias E.S., Lilley C., Armengol L., Spysschaert Y., Verloo P., De Coene A., Goossens L., Mortier G., Speleman F., van Binsbergen E., Nelen M.R., Hochstenbach R., Poot M., Gallagher L., Gill M., McClellan J., King M.C., Regan R., Skinner C., Stevenson R.E., Antonarakis S.E., Chen C., Estivill X., Menten B., Gimelli G., Gribble S., Schwartz S., Sutcliffe J.S., Walsh T., Knight S.J., Sebat J., Romano C., Schwartz C.E., Veltman J.A., de Vries B.B., Vermeesch J.R., Barber J.C., Willatt L., Tassabehji M., Eichler E.E. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N. Engl. J. Med. 2008, 359:1685-1699.
13. Megarbane A., Cormier-Daire V. Severe mental retardation, short stature, facial anomalies, joint laxity, and dislocations in two sisters: previously undescribed MCA/MR syndrome. Am. J. Med. Genet. 2001, 102:153-156.
14. Megarbane A., Dagher R., Melki I. Sib pair with previously unreported skeletal dysplasia. Am. J. Med. Genet. A 2008, 146A:2916-2919.
15. Nobrega M.A., Zhu Y., Plajzer-Frick I., Afzal V., Rubin E.M. Megabase deletions of gene deserts result in viable mice. Nature 2004, 431:988-993.
16. Sharp A.J., Hansen S., Selzer R.R., Cheng Z., Regan R., Hurst J.A., Stewart H., Price S.M., Blair E., Hennekam R.C., Fitzpatrick C.A., Segraves R., Richmond T.A., Guiver C., Albertson D.G., Pinkel D., Eis P.S., Schwartz S., Knight S.J., Eichler E.E. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nat. Genet. 2006, 38:1038-1042.
17. Sharp A.J., Mefford H.C., Li K., Baker C., Skinner C., Stevenson R.E., Schroer R.J., Novara F., De Gregori M., Ciccone R., Broomer A., Casuga I., Wang Y., Xiao C., Barbacioru C., Gimelli G., Bernardina B.D., Torniero C., Giorda R., Regan R., Murday V., Mansour S., Fichera M., Castiglia L., Failla P., Ventura M., Jiang Z., Cooper G.M., Knight S.J., Romano C., Zuffardi O., Chen C., Schwartz C.E., Eichler E.E. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat. Genet. 2008, 40:322-328.
18. Uz E., Alanay Y., Aktas D., Vargel I., Gucer S., Tuncbilek G., von Eggeling F., Yilmaz E., Deren O., Posorski N., Ozdag H., Liehr T., Balci S., Alikasifoglu M., Wollnik B., Akarsu N.A. Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia. Am. J. Hum. Genet. 2010, 86:789-796.
19. Vissers L.E., de Ligt J., Gilissen C., Janssen I., Steehouwer M., de Vries P., van Lier B., Arts P., Wieskamp N., del Rosario M., van Bon B.W., Hoischen A., de Vries B.B., Brunner H.G., Veltman J.A. A de novo paradigm for mental retardation. Nat. Genet. 2010, 42:1109-1112.
20. Wong K.K., de Leeuw R.J., Dosanjh N.S., Kimm L.R., Cheng Z., Horsman D.E., MacAulay C., Ng R.T., Brown C.J., Eichler E.E., Lam W.L. A comprehensive analysis of common copy-number variations in the human genome. Am. J. Hum. Genet. 2007, 80:91-104.
21. Young I.D. Introduction of Risk Calculation in Genetic Counseling 1999, Oxford University Press.