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Nail‑Patella syndrome with early onset end‑stage renal disease in a child with a novel heterozygous missense mutation in the LMX1B homeodomain: A case report

  • Authors:
    • Soledad Carinelli
    • Olalla Alvarez Blanco
    • Ana  Perdomo‑Ramirez
    • Felix Claverie‑Martin
  • View Affiliations / Copyright

    Affiliations: Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain, Nefrologia Infantil, Hospital General Univesitario Gregorio Marañón, 28007 Madrid, Spain
    Copyright: © Carinelli et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 49
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    Published online on: September 4, 2020
       https://doi.org/10.3892/br.2020.1356
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Abstract

Nail‑Patella syndrome (NPS) is an inherited disease characterized by nail and skeletal anomalies, nephropathy and glaucoma. The diagnosis of NPS is based on clinical findings, including hypoplastic or absent patella, dystrophic nails, dysplasia of the elbows and iliac horns. However, the main determinant of NPS prognosis is nephropathy, which may range from asymptomatic proteinuria to end‑stage renal disease. NPS is caused by heterozygous loss‑of‑function mutations in the LMX1B gene, which encodes the LIM homeodomain transcription factor LMX1B. LMX1B serves an essential role in the physiological development of dorsal‑ventral limb structures, morphogenesis and function of podocytes, as well as in development of the anterior segments of the eyes, and in certain types of neurons. The present study aimed to identify the disease‑causing mutation in a 2‑year old girl with nephrotic syndrome that evolved rapidly to end‑stage renal disease. The patient showed classical symptoms of NPS including dystrophic nails and an absence of the patellae. DNA sequence analysis identified a novel missense variant in exon 4 of LMX1B (c.709T>C, p.S237P); this substitution affected a conserved serine residue in the homeodomain of LMX1B and was predicted to be pathogenic. In silico modeling of the homeodomain revealed that the p.S237P mutation converted the A236‑S237‑F238 segment of α‑helix 1 into a strand. It was hypothesized that this mutation affected binding of the transcription factor to its target DNA, thus abrogating transcription activation, which would explain the phenotype that manifested in the patient.
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Copy and paste a formatted citation
Spandidos Publications style
Carinelli S, Blanco OA, Perdomo‑Ramirez A and Claverie‑Martin F: Nail‑Patella syndrome with early onset end‑stage renal disease in a child with a novel heterozygous missense mutation in the LMX1B homeodomain: A case report. Biomed Rep 13: 49, 2020.
APA
Carinelli, S., Blanco, O.A., Perdomo‑Ramirez, A., & Claverie‑Martin, F. (2020). Nail‑Patella syndrome with early onset end‑stage renal disease in a child with a novel heterozygous missense mutation in the LMX1B homeodomain: A case report. Biomedical Reports, 13, 49. https://doi.org/10.3892/br.2020.1356
MLA
Carinelli, S., Blanco, O. A., Perdomo‑Ramirez, A., Claverie‑Martin, F."Nail‑Patella syndrome with early onset end‑stage renal disease in a child with a novel heterozygous missense mutation in the LMX1B homeodomain: A case report". Biomedical Reports 13.5 (2020): 49.
Chicago
Carinelli, S., Blanco, O. A., Perdomo‑Ramirez, A., Claverie‑Martin, F."Nail‑Patella syndrome with early onset end‑stage renal disease in a child with a novel heterozygous missense mutation in the LMX1B homeodomain: A case report". Biomedical Reports 13, no. 5 (2020): 49. https://doi.org/10.3892/br.2020.1356
Copy and paste a formatted citation
x
Spandidos Publications style
Carinelli S, Blanco OA, Perdomo‑Ramirez A and Claverie‑Martin F: Nail‑Patella syndrome with early onset end‑stage renal disease in a child with a novel heterozygous missense mutation in the LMX1B homeodomain: A case report. Biomed Rep 13: 49, 2020.
APA
Carinelli, S., Blanco, O.A., Perdomo‑Ramirez, A., & Claverie‑Martin, F. (2020). Nail‑Patella syndrome with early onset end‑stage renal disease in a child with a novel heterozygous missense mutation in the LMX1B homeodomain: A case report. Biomedical Reports, 13, 49. https://doi.org/10.3892/br.2020.1356
MLA
Carinelli, S., Blanco, O. A., Perdomo‑Ramirez, A., Claverie‑Martin, F."Nail‑Patella syndrome with early onset end‑stage renal disease in a child with a novel heterozygous missense mutation in the LMX1B homeodomain: A case report". Biomedical Reports 13.5 (2020): 49.
Chicago
Carinelli, S., Blanco, O. A., Perdomo‑Ramirez, A., Claverie‑Martin, F."Nail‑Patella syndrome with early onset end‑stage renal disease in a child with a novel heterozygous missense mutation in the LMX1B homeodomain: A case report". Biomedical Reports 13, no. 5 (2020): 49. https://doi.org/10.3892/br.2020.1356
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