Identification of entire LMX1B gene deletions in nail patella syndrome: Evidence for haploinsufficiency as the main pathogenic mechanism underlying dominant inheritance in man

European Journal of Human Genetics

Volumn 16, Issue 10, 2008, Pages 1240-1244

  Bongers, Ernie M H F ^a   de Wijs, Ilse J ^a   Marcelis, Carlo ^a   Hoefsloot, Lies H ^a   Knoers, Nine V A M ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

HOMEODOMAIN PROTEIN; TRANSCRIPTION FACTOR LMX1B; UNCLASSIFIED DRUG;

ARTICLE; CLINICAL ARTICLE; DOMINANT INHERITANCE; EXON; FAMILY STUDY; GENE AMPLIFICATION; GENE DELETION; GENE FUNCTION; GENE MUTATION; GENE PROBE; GENETIC ANALYSIS; GENETIC DISORDER; HETEROZYGOSITY; HUMAN; MUTATIONAL ANALYSIS; NAIL PATELLA SYNDROME; PHENOTYPIC VARIATION; PRIORITY JOURNAL; SEQUENCE ANALYSIS;

CHROMOSOMES, HUMAN, PAIR 9; FEMALE; GENE DELETION; GENES, DOMINANT; HAPLOIDY; HOMEODOMAIN PROTEINS; HUMANS; INHERITANCE PATTERNS; MALE; NAIL-PATELLA SYNDROME; PEDIGREE; POLYMERASE CHAIN REACTION; TRANSCRIPTION FACTORS;

ANIMALIA; MUS;

EID: 53249098488     PISSN: 10184813     EISSN: 14765438     Source Type: Journal    
DOI: 10.1038/ejhg.2008.83     Document Type: Article

References (27)

1. Dreyer SD, Zhou G, Baldini A et al: Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. Nat Genet 1998; 19: 47-50.
2. Vollrath D, Jaramillo-Babb VL, Clough MV et al: Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome. Hum Mol Genet 1998; 7: 1091-1098.
3. Clough MV, Hamlington JD, McIntosh I: Restricted distribution of loss-of-function mutations within the LMX1B genes of nail-patella syndrome patients. Hum Mutat 1999; 14: 459-465.
4. McIntosh I, Dreyer SD, Clough MV et al: Mutation analysis of LMX1B gene in nail-patella syndrome patients. Am J Hum Genet 1998; 63 1651-1658.
5. Seri M, Metchionda S, Dreyer S et al: Identification of LMX1B gene point mutations in italian patients affected with Nail-Patella syndrome. Int J Mol Med 1999; 4: 285-290.
6. Knoers NV, Bongers EM, van Beersum SE, Lommen EJ, van Bokhoven H, Hol FA: Nail-patella Iyndrome: identification of mutations in the LMX1B gene in Dutch families. J Am Soc Nephrol 2000; 11: 1762-1766.
7. Hamlington JD, Jones C, McIntosh I: Twenty-two novel LMX1B mutations identified in nail patella syndrome (NPS) patients. Hum Mutat 2001; 18: 458.
8. Bongers EM, Gubler MC, Knoers NV: Nail-patella syndrome. Overview on clinical and molecular findings. Pediatr Nephrol 2002; 17: 703-712.
9. Bongers EM, Huysmans FT, Levtchenko E et al. Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy. Eur J Hum Genet 2005; 13: 935-946.
10. Dunston JA, Hamlington JD, Zaveri J et al: The human LMX1B gene: transcription unit, promoter, and pathogenic mutations. Genomics 2004; 84: 565-576.
11. Hamlington JD, Clough MV, Dunston JA, McIntosh I: Deletion of a branch-point consensus sequence in the LMX1B gene causes exon skipping in a family with nail patella syndrome. Eur J Hum Genet 2000; 8 311-314.
12. Silahtaroglu A, Hol FA, Jensen PK et al: Molecular cytogenetic detection of 9q34 breakpoints associated with nail patella syndrome. Eur J Hum Genet 1999; 7: 68-76.
13. Endele S, Klein S, Richter S et al: Renal phenotype in heterozygous Lmx1b knockout mice (Ln1x1b (+/-)) after unilateral nephrectomy. Transgenic Res 2007; 16: 723-729.
14. Miner JH, Morello R, Andrews KL et al: Transcriptional induction of slit diaphragm genes by Lmx1b is required in podocyte differentiation. J Clin Invest 2002; 109: 1065-1072.
15. Morello, R, Zhou G, Dreyer SD et al: Regulation of glomendar basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome. Nat Genet 2001; 27: 205-208.
16. Rohr C, Prestel J, Heidet L et al: The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes. J Clin Invest 2002; 109: 1073-1082.
17. Suleiman H, Heudobler D, Raschta AS et al: The podocyte-specific inactivation of Lmx1b, Ldb1 and E2a yields new insight into a transcriptional network in podocytes. Dev Biol 2007; 304: 701-712.
18. Pressman CL, Chen H, Johnson RL: LMX1B, a LIM homeodomain class transcription factor, is necessary for normal development of multiple tissues in the anterior segment of the murine eye. Genesis 2000; 26: 15-25.
19. Smidt MP, Asbreuk CH, Cox JJ, Chen H, Johnson RL, Burbach JP: A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b. Nat Neurosci 2000; 3: 337-341.
20. Chen H, Lun Y, Ovchinnikov D et al: Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome. Nat Genet 1998; 19: 51-55.
21. Sato U, Kitanaka S, Sekine T, Takahashi S, Ashida A, Igarashi T: Functional characterization of LMX1B mutations associated with nail-patella syndrome. Pediatr Res 2005; 57: 783-788.
22. Dreyer SD, Morello, R, German MS et al: LMX1B transactivation and expression in nail-patella syndrome. Hum Mol Genet 2000; 9: 1067-1074.
23. Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G: Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification1. Nucleic Acids Res 2002; 30: E57.
24. White SJ, Vink GR, Kriek M et al: Two-color multiplex ligation-dependent probe amplification: Detecting genomic rearrangements in hereditary pultiple exostoses. Hum Mutat 2004; 24: 86-92.
25. Behm-Ansmant I, Kashima I, Rehwinkel J, Sauliere J, Wittkopp N, Izaurralde E: MRAA quality control: an ancient machinery recognizes and degrades mRNAs with nonsense codons. FEBS Lett 2007; 581: 2845-2853.
26. Schlaubitz S, Yatsenko SA, Smith LD et al: Ovotestes and XY sex reversal in a female with an interstitial 9q33.3-q34.1 deletion encompassing NRSA1 and LMX1B causing features of Genitopatellar syndrome. Am J Med Genet A 2007; 143: 1071-1081.
27. Morello, R, Dreyer S, Oberg KC, Lee B: Localization of Lmx1b during kidney and limb development and pathogenesis of nail patella syndrome. Am J Hum Genet 1999; 65S: A77.