Truncating mutations in LRP4 lead to a prenatal lethal form of Cenani-Lenz syndrome

American Journal of Medical Genetics, Part A

Volumn 164, Issue 9, 2014, Pages 2391-2397

  Lindy, Amanda S ^a   Bupp, Caleb P ^a   Mcgee, Stephen J ^a   Steed, Erin ^a   Stevenson, Roger E ^a   Basehore, Monica J ^a   Friez, Michael J ^a  

^a GREENWOOD GENETIC CENTER   (United States)

Author keywords

Cenani Lenz syndrome; Fetal demise; Limb development; Low density lipoprotein; LRP4; Syndactyly

Indexed keywords

ARTICLE; AUTOSOMAL RECESSIVE DISORDER; BONE DYSPLASIA; CASE REPORT; CENANI LENZ SYNDROME; FETUS; GENE; GENE MUTATION; GENOTYPE PHENOTYPE CORRELATION; HEART VENTRICLE SEPTUM DEFECT; HETEROZYGOSITY; HUMAN; KIDNEY MALFORMATION; LETHALITY; LRP4 GENE; MICROGNATHIA; MUTATIONAL ANALYSIS; NOSE MALFORMATION; OLIGOHYDRAMNIOS; OLIGOSYNDACTYLY; PHOCOMELIA; PRENATAL DISORDER; PRIORITY JOURNAL; RADIOGRAPHY; SKIN EDEMA; SYNDACTYLY; THORAX MALFORMATION; VAGINA ATRESIA; CONGENITAL MALFORMATION; FATALITY; FEMALE; GENETICS; MALE; MUTATION; PEDIGREE; POSTMORTEM CHANGE; SIBLING;

LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; LRP4 PROTEIN, HUMAN;

FATAL OUTCOME; FEMALE; FETUS; HUMANS; LDL-RECEPTOR RELATED PROTEINS; MALE; MUTATION; PEDIGREE; POSTMORTEM CHANGES; SIBLINGS; SYNDACTYLY;

EID: 84905903118     PISSN: 15524825     EISSN: 15524833     Source Type: Journal    
DOI: 10.1002/ajmg.a.36647     Document Type: Article

References (19)

1. Bodine PV. 2008. WNT signaling control of bone cell apoptosis. Cell Res 18:248-253.
2. Cenani A, Lenz W. 1967. Total syndactylia and total radioulnar synostosis in 2 brothers. A contribution on the genetics of syndactylia. Z Kinderheilkd 101:181-190.
3. Clevers H. 2006. WNT/beta-catenin signaling in development and disease. Cell 127:469-480.
4. Dietrich MF, van der Weyden L, Prosser HM, Bradley A, Herz J, Adams DJ. 2010. Ectodomains of the LDL receptor-related proteins LRP1B and LRP4 have anchorage independent functions in vivo. PLoS ONE 5:e9960.
5. Elcioglu N, Atasu M, Cenani A. 1997. Dermatoglyphics in patients with Cenani-Lenz type syndactyly: Studies in a new case. Am J Med Genet 70:341-345.
6. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML. Osteoporosis-pseudoglioma syndrome collaborative G. 2001. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513-523.
7. Gordon MD, Nusse R. 2006. WNT signaling: Multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem 281:22429-22433.
8. Jarbhou H, Hamamy H, Al-Hadidy A, Ajlouni K. 2008. Cenani-Lenz syndactyly with facial dysmorphism, hypothyroidism, and renal hypoplasia: A case report. Clin Dysmorphol 17:269-270.
9. Johnson EB, Hammer RE, Herz J. 2005. Abnormal development of the apical ectodermal ridge and polysyndactyly in megf7-deficient mice. Hum Mol Genet 14:3523-3538.
10. Johnson EB, Steffen DJ, Lynch KW, Herz J. 2006. Defective splicing of megf7/lrp4, a regulator of distal limb development, in autosomal recessive mulefoot disease. Genomics 88:600-609.
11. Kariminejad A, Stollfuss B, Li Y, Bogershausen N, Boss K, Hennekam RC, Wollnik B. 2013. Severe Cenani-Lenz syndrome caused by loss of LRP4 function. Am J Med Genet Part A 161A:1475-1479.
12. Karner CM, Dietrich MF, Johnson EB, Kappesser N, Tennert C, Percin F, Wollnik B, Carroll TJ, Herz J. 2010. Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation-A mouse model for Cenani-Lenz syndrome. PLoS ONE 5:e10418.
13. Khan TN, Klar J, Ali Z, Khan F, Baig SM, Dahl N. 2013. Cenani-Lenz syndrome restricted to limb and kidney anomalies associated with a novel LRP4 missense mutation. Eur J Med Genet 56:371-374.
14. Leupin O, Piters E, Halleux C, Hu S, Kramer I, Morvan F, Bouwmeester T, Schirle M, Bueno-Lozano M, Fuentes FJ, Itin PH, Boudin E, de Freitas F, Jennes K, Brannetti B, Charara N, Ebersbach H, Geisse S, Lu CX, Bauer A, Van Hul W, Kneissel M. 2011. Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem 286(22):19489-19500.
15. Li Y, Pawlik B, Elcioglu N, Aglan M, Kayserili H, Yigit G, Percin F, Goodman F, Nurnberg G, Cenani A, Urquhart J, Chung BD, Ismail S, Amr K, Aslanger AD, Becker C, Netze C, Scambler P, Eyaid W, Hamamy H, Clayton-Smith J, Hennekam R, Nurnberg P, Herz J, Temtamy SA, Wollnik B. 2010. LRP4 mutations alter WNT/beta-catenin signaling and cause limb and kidney malformations in Cenani-Lenz syndrome. Am J Hum Genet 86:696-706.
16. Logan CY, Nusse R. 2004. The WNT signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781-810.
17. Mani A, Radhakrishnan J, Wang H, Mani A, Mani MA, Nelson-Williams C, Carew KS, Mane S, Najmabadi H, Wu D, Lifton RP. 2007. LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science 315:1278-1282.
18. Ohazama A, Johnson EB, Ota MS, Choi HY, Porntaveetus T, Oommen S, Itoh N, Eto K, Gritli-Linde A, Herz J, Sharpe PT. 2008. LRP4 modulates extracellular integration of cell signaling pathways in development. PLoS ONE 3:e4092.
19. Temtamy SA, Ismail S, Nemat A. 2003. Mild facial dysmorphism and quasidominant Inheritance in Cenani-Lenz syndrome. Clin Dysmorphol 12:77-83.