Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV are caused by genomic duplications involving the long range, limb-specific SHH enhancer

Journal of Medical Genetics

Volumn 45, Issue 9, 2008, Pages 589-595

  Sun, M ^a   Ma, F ^a   Zeng, X ^b   Liu, Q ^a   Zhao, X L ^a   Wu, F X ^c   Wu, G P ^d   Zhang, Z F ^e   Gu, B ^f   Zhao, Y F ^g   Tian, S H ^h   Lin, B ⁱ   Kong, X Y ⁱ   Zhang, X L ^a   Yang, W ^a   Lo, W H Y ^a   Zhang, Xue ^a  

^a INSTITUTE OF BASIC MEDICAL SCIENCES   (China)

^b PEKING UNION MEDICAL COLLEGE HOSPITAL   (China)

^c JINZHOU MEDICAL UNIVERSITY   (China)

^d SOUTHWEST MEDICAL UNIVERSITY   (China)

^e PLA No 148 Hospital   (China)

^f Sichuan Huamei Zixin Medicine Aesthetic Hospital   (China)

^g FOURTH MILITARY MEDICAL UNIVERSITY   (China)

^h QIQIHAR MEDICAL UNIVERSITY   (China)

ⁱ Shanghai Jiao Tong University Affiliated Sixth People s Hospital   (China)

Author keywords

[No Author keywords available]

Indexed keywords

SONIC HEDGEHOG PROTEIN;

ALLELE; ARTICLE; AUTOSOMAL DOMINANT DISORDER; CHINESE; CONTROLLED STUDY; FAMILY; FLUORESCENCE IN SITU HYBRIDIZATION; GENE DUPLICATION; GENE LOCUS; GENE MAPPING; GENETIC LINKAGE; HAPLOTYPE; HETEROZYGOSITY; HUMAN; MAJOR CLINICAL STUDY; PATHOGENESIS; PHENOTYPE; POINT MUTATION; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; SINGLE NUCLEOTIDE POLYMORPHISM; SYNDACTYLY; SYNDACTYLY TYPE 4; TRIPHALANGEAL THUMB POLYSYNDACTYLY SYNDROME;

ALLELIC IMBALANCE; ENHANCER ELEMENTS (GENETICS); FINGERS; GENOME, HUMAN; HAPLOTYPES; HEDGEHOG PROTEINS; HUMANS; IN SITU HYBRIDIZATION, FLUORESCENCE; LINKAGE (GENETICS); MUTATION; PEDIGREE; PHENOTYPE; POINT MUTATION; SYNDACTYLY; SYNDROME; THUMB;

ERINACEIDAE;

EID: 51849131025     PISSN: 00222593     EISSN: None     Source Type: Journal    
DOI: 10.1136/jmg.2008.057646     Document Type: Article

References (29)

1. Hill RE. How to make a zone of polarizing activity: insights into limb development via the abnormality preaxial polydactyly. Dev Growth Differ 2007;49:439-48.
2. Heutink P, Zguricas J, van Oosterhout L, Breedveld GJ, Testers L, Sandkuijl LA, Snijders PJ, Weissenbach J, Lindhout D, Hovius SE, Oostra BA. The gene for triphalangeal thumb maps to the subtelomeric region of chromosome 7q. Nat Genet 1994;6:287-92.
3. Hing AV, Helms C, Slaugh R, Burgess A, Wang JC, Herman T, Dowton SB, Donis-Keller H. Linkage of preaxial polydactyly type 2 to 7q36. Am J Med Genet 1995;58:128-35.
4. Radhakrishna U, Blouin JL, Solanki JV, Dhoriani GM, Antonarakis SE. An autosomal dominant triphalangeal thumb: polysyndactyly syndrome with variable expression in a large Indian family maps to 7q36. Am J Med Genet 1996;66:209-15.
5. Zguricas J, Heus H, Morales-Peralta E, Breedveld G, Kuyt B, Mumcu E, Bakker W, Akarsu N, Kay S, Hovius S, Heredero-Baute L, Oostra B, Heutink P. Clinical and genetic studies on 12 preaxial polydactyly families and refinement of the localisation of the gene responsible to a 1.9 cM region on chromosome 7q36. J Med Genet 1999;36:3240.
6. Heus HC, Hing A, van Baren MJ, Joosse M, Breedveld GJ, Wang JC, Burgess A, Donnis-Keller H, Berglund C, Zguricas J, Scherer SW, Rommens JM, Oostra BA, Heutink P. A physical and transcriptional map of the preaxial polydactyly locus on chromosome 7q36. Genomics 1999; 57:342-51.
7. Dobbs MB, Dietz FR, Gurnett CA, Morcuende JA, Steyers CM, Murray JC. Localization of dominantly inherited isolated triphalangeal thumb to chromosomal region 7q36. J Orthop Res 2000;18:340-4.
8. Lettce LA, Horikoshi T, Heaney SJ, van Baren MJ, van der Linde HC, Breedveld GJ, Joosse M, Akarsu N, Oostra BA, Endo N, Shibata M, Suzuki M, Takahashi E, Shinka T, Nakahori Y, Ayusawa D, Nakabayashi K, Scherer SW, Heutink P, Hill RE, Noji S. Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly. Proc Natld Acad Sci USA 2002;99:7548-53.
9. Lenice LA, Heaney SJ, Purdie LA, Li L, de Beer P, Oostra BA, Goode D, Elgar G, Hill RE, de Graaff E. A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum Mol Genet 2003;12:1725-35.
10. Sagai T, Masuya H, Tamura M, Shimizu K, Yada Y, Wakana S, Gondo Y, Node T, Shiroishi T. Phylogenetic conservation of a limb-specific, cis-acting regulator of Sonic hedgehog (Shh). Mamm Genome 2004; 15:23-34
11. Gurnett CA, Bowcock AM, Dietz FR, Morcuende JA, Murray JC, Dobbs MB. Two novel point mutations in the long-range SHH enhancer in three families with triphalangeal thumb and preaxial polydactyly. Am J Med Genet A 2007;143:27-32.
12. Masuya H, Sezutsu H, Sakuraba Y, Sagai T, Hosoya M, Kaneda H, Miura I, Kobayashi K, Sumiyama K, Shimizu A, Nagano J, Yokoyama H, Kaneko S, Sakurai N, Okagaki Y, Noda T, Wakana S, Gondo Y, Shiroishi T. A series of ENU-induced single-base substitutions in a long-range cis-element altering Sonic hedgehog expression in the developing mouse limb bud. Genomics 2007;89:207-14.
13. Lettice LA, Hill AE, Devenney PS, Hill R. Point mutations in a distant Sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly. Hum Mol Genet 2008; 17:978-85.
14. Tsukurov O, Boehmer A, Flynn J, Nicolai JP, Hamel BC, Traill S, Zaleske D, Mankin HJ, Yeon H, Ho C, Tabin C, Seidman JG, Seidman C. A complex bilateral polysyndactyly disease locus maps to chromosome 7q36. Nature Genet 1994:6;282-6.
15. Balci S, Demirtas M, Civelek B, Piskin M, Sensoz O, Akarsu AN. Phenotypic variability of triphalangeal thumb-polysyndactyly syndrome linked to chromosome 7q36. Am J Med Genet 1999;87:399-406.
16. Wang ZQ, Tian SH, Shi YZ, Zhou PT, Wang ZY, Shu RZ, Hu L, Kong X. A single C to T transition in intrion 5 of LMBR1 gene is associated with triphalangeal thumb-polysyndactyly syndrome in a Chinese family. Biochem Biophys Res Commun 2007;355:312-7.
17. Sato D, Liang D, Wu L, Pan Q, Xia K, Dai H, Wang H, Nishimura G, Yoshiura K, Xia J, Niikawa N. A syndactyly type IV locus maps to 7q36. J Hum Genet 2007;52:561-4.
18. Zhao X, Sun M, Zhao J, Leyva JA, Zhu H, Yang W, Zeng X, Ao Y, Liu Q, Liu G, Lo WH, Jabs EW, Amzel LM, Shan X, Zhang X. Mutations in HOXD13 underlie syndactyly type V and a novel brachydactyly-syndactyly syndrome. Am J Hum Genet 2007;80:361-71.
19. Lyle R, Radhakrishna U, Blouin JL, Gagos S, Everman DB, Gehrig C, Delozier-Blanchet C, Solanki JV, Patel UC, Nath SK, Gurrieri F, Neri G, Schwartz CE, Antonarakis SE. Split-hand/split-foot malformation 3 (SHFM3) at 10q24, development of rapid diagnostic methods and gene expression from the region. Am J Med Genet A 2006; 140:1384-95.
20. Sharpe J, Lattice L, Hecksher-Sorensen J, Fox M, Hill R, Krumlauf R. Identification of sonic hedgehog as a candidate gene responsible for the polydactylous mouse mutant Sasquatch. Curr Biol 1999; 9:97-100.
21. Klopocki E, Ott CE, Benatar N, Ullmann R, Mundlos S, Lehmann K. A microduplication of the long range SHH limb regulator (ZFS) is associated with triphalangeal thumb-polysyndactyly syndrome. J Med Genet 2008;45:370-5.
22. Heus HC, Luijsterburg AJ, van Baren MJ, Breedveld CJ, Joosse MN, Nieuwenhuizen IM, Vermeij-Keers C, Oostro BA, Heutink P. Hemimelic extra toes and Hammer toe are distinct mutations that show a genetic interaction. Mamm Genome 2001;12:77-9.
23. Clark RM, Marker PC, Kingsley DM. A novel candidate gene for mouse and human preaxial polydactyly with altered expression in limbs of Hemimelic extra-toes mutant mice. Genomics 2000;67:19-27.
24. Ianakiev P, van Baren MJ, Daly MJ, Toledo SP, Cavalcanti MG, Neto JC, Silveira EL, Freire-Maia A, Heutink P, Kilpatrick MW, Tsipouras P. Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene. Am J Hum Genet 2001;68:38-45.
25. Goode DK, Snell P, Smith SF, Cooke JE, Elgar G. Highly conserved regulatory elements around the SHH gene may contribute to the maintenance of conserved synteny across human chromosome 7q36.3. Genomics 2005;86:172-81.
26. Kantaputra PN, Chalidapong P. Are triphalangeal thumb-polysyndactyly syndrome (TPTPS) and tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome (THPTTS) identical? A father with TPTPS and his daughter with THPTTS in a Thai family. Am J Med Genet 2000:93: 126-31.
27. Dundar M, Gordon TIM, Ozyazgan I, Oguzkaya F, Ozkul Y, Cooke A, Wilkinson AG, Holloway S, Goodman FR, Tolmie JL. A novel acropectoral syndrome maps to chromosome 7q36. J Med Genet 2001; 38:304-9.
28. Beckmann JS, Estivill X, Antonarakis SE. Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability. Nat Rev Genet 2007;8:639-46.
29. Feuk L, Carson AR, Scherer SW. Structural variation in the human genome. Nat Rev Genet 2006;7:85-97.