A Novel ZRS Mutation Leads to Preaxial Polydactyly Type 2 in a Heterozygous Form and Werner Mesomelic Syndrome in a Homozygous Form

Human Mutation

Volumn 35, Issue 8, 2014, Pages 945-948

  Vandermeer, Julia E ^a,b   Lozano, Reymundo ^c   Sun, Miao ^d,e   Xue, Yuan ^f   Daentl, Donna ^g   Jabs, Ethylin Wang ^e,h   Wilcox, William R ^f   Ahituv, Nadav ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIVERSITY   (China)

^e JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g SHRINERS HOSPITALS FOR CHILDREN NORTHERN CALIFORNIA   (United States)

^h MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Enhancer; Preaxial polydactyly; SHH; Werner mesomelic syndrome; ZRS

Indexed keywords

LMBR1 PROTEIN, HUMAN; MEMBRANE PROTEIN;

ANIMAL; CONGENITAL MALFORMATION; FEMALE; GENE DOSAGE; GENETICS; GENOTYPE; HAND MALFORMATION; HETEROZYGOTE; HOMOZYGOTE; HUMAN; MEXICO; MOLECULAR GENETICS; MOUSE; MUTATION; NUCLEOTIDE SEQUENCE; PATHOLOGY; PEDIGREE; PHENOTYPE; POLYDACTYLY; THUMB;

ANIMALS; BASE SEQUENCE; FEMALE; GENE DOSAGE; GENOTYPE; HAND DEFORMITIES, CONGENITAL; HETEROZYGOTE; HOMOZYGOTE; HUMANS; MEMBRANE PROTEINS; MEXICO; MICE; MOLECULAR SEQUENCE DATA; MUTATION; PEDIGREE; PHENOTYPE; POLYDACTYLY; THUMB;

EID: 84904428732     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.22581     Document Type: Article

References (17)

1. Albuisson J, Isidor B, Giraud M, Pichon O, Marsaud T, David A, Le Caignec C, Bezieau S. 2010. Identification of two novel mutations in Shh long-range regulator associated with familial pre-axial polydactyly. Clin Genet 79:371-377.
2. Amano T, Sagai T, Tanabe H, Mizushina Y, Nakazawa H, Shiroishi T. 2009. Chromosomal dynamics at the Shh locus: limb bud-specific differential regulation of competence and active transcription. Dev Cell 16:47-57.
3. Farooq M, Troelsen JT, Boyd M, Eiberg H, Hansen L, Hussain MS, Rehman SU, Azhar A, Ali A, Bakhtiar SM, Tommerup N, Baig SM, et al. 2010. Preaxial polydactyly/triphalangeal thumb is associated with changed transcription factor-binding affinity in a family with a novel point mutation in the long-range cis-regulatory element ZRS. Eur J Hum Genet 18:733-736.
4. Furniss D, Lettice LA, Taylor IB, Critchley PS, Giele H, Hill RE, Wilkie AOM. 2008. A variant in the sonic hedgehog regulatory sequence (ZRS) is associated with triphalangeal thumb and deregulates expression in the developing limb. Hum Mol Genet 17:2417-2423.
5. Gurnett CA, Bowcock AM, Dietz FR, Morcuende JA, Murray JC, Dobbs MB. 2007. Two novel point mutations in the long-range SHH enhancer in three families with triphalangeal thumb and preaxial polydactyly. Am J Med Genet 143A:27-32.
6. Kel AE, Gobling E, Reuter I, Cheremushkin E, Kel-Margoulis OV, Wingender E. 2003. MATCH: a tool for searching transcription factor binding sites in DNA sequences. Nucleic Acids Res 31:3576-3579.
7. Laurell T, VanderMeer JE, Wenger AM, Grigelioniene G, Nordenskjöld A, Arner M, Ekblom AG, Bejerano G, Ahituv N, Nordgren A. 2012. A novel 13 base pair insertion in the sonic hedgehog ZRS limb enhancer (ZRS/LMBR1) causes preaxial polydactyly with triphalangeal thumb. Hum Mutat 33:1063-1066.
8. Lettice LA, Heaney SJH, Purdie LA, Li L, de Beer P, Oostra BA, Goode D, Elgar G, Hill RE, de Graaff E. 2003. A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum Mol Genet 12:1725-1735.
9. Lettice LA, Hill AE, Devenney PS, Hill RE. 2008. Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly. Hum Mol Genet 17:978-985.
10. Moore K, Persaud T. 1998. The developing human: Clinically oriented embryology. Philadelphia, Pennsylvania: Saunders.
11. Park K, Kang J, Subedi KP, Ha JH, Park C. 2008. Canine polydactyl mutations with heterogeneous origin in the conserved intronic sequence of LMBR1. Genetics 179:2163-2172.
12. Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, Plajzer-Frick I, Akiyama J, et al. 2006. In vivo enhancer analysis of human conserved non-coding sequences. Nature 444:499-502.
13. Saunders JW, Gasseling, MT. 1968. Ectodermal-mesenchymal interactions in the origin of limb symmetry. In: Rleischmajar F, Billingham RE, editors. Epithelial-mesenchymal interactions. Baltimore, Maryland: Williams and Wilkins. p 78-97.
14. Semerci CN, Demirkan F, Ozdemir M, Biskin E, Akin B, Bagci H, Akarsu NA. 2009. Homozygous feature of isolated triphalangeal thumb-preaxial polydactyly linked to 7q36: no phenotypic difference between homozygotes and heterozygotes. Clin Genet 76:85-90.
15. Sun M, Ma F, Zeng X, Liu Q, Zhao XL, Wu FX, Wu GP, Zhang ZF, Gu B, Zhao YF, Tian SH, Lin B, et al. 2008. Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV are caused by genomic duplications involving the long range, limb-specific SHH enhancer. J Med Genet 45:589-595.
16. VanderMeer JE, Ahituv N. 2011. cis-Regulatory mutations are a genetic cause of human limb malformations. Dev Dyn 240:920-930.
17. Wieczorek D, Pawlik B, Li Y, Akarsu NA, Caliebe A, May KJW, Schweiger B, Vargas FR, Balci S, Gillessen-Kaesbach G, Wollnik B. 2009. A specific mutation in the distant Sonic Hedgehog (SHH) cis-regulator (ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie Haas type polysyndactyly and preaxial polydactyly (PPD) with or without triphalangeal thumb. Hum Mutat 31:81-89.