J Pediatr Genet 2019; 08(03): 163-167
DOI: 10.1055/s-0039-1684017
Case Report
Georg Thieme Verlag KG Stuttgart · New York

Report of Two Novel Mutations in Indian Patients with Rothmund–Thomson Syndrome

Sakshi Yadav
1   Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
,
Seema Thakur
2   Division of Genetic and Fetal Medicine, Fortis Hospital, Delhi and Apollo Hospital, New Delhi, India
,
Juergen Kohlhase
3   SYNLAB MVZ Humangenetik Freiburg GmbH, Germany
,
Neetu Bhari
4   Department of Skin, All India Institute of Medical Sciences, New Delhi, India
,
Madhulika Kabra
1   Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
,
1   Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
› Author Affiliations
Further Information

Publication History

02 July 2018

23 February 2019

Publication Date:
09 April 2019 (online)

Abstract

Rothmund–Thomson syndrome (RTS) is a rare autosomal recessive disorder caused by mutations in RECQL4 and has characteristic clinical features. We report two unrelated phenotypically diverse patients (cases 1 and 2) with RTS having novel variants in RECQL4 gene. Case-1 was evaluated for poor growth and recurrent fractures and skin lesions. Case-2 presented at 4 months with failure to thrive and radial ray defect and developed poikilodermatous skin lesions after infancy. Both cases were confirmed to have homozygous pathogenic variants in RECQL4. Both patients have normal intellect and are on supportive therapy. The presence of characteristic poikiloderma lesions with specific distribution and skeletal anomalies in a patient with proportionate short stature is a clue toward the diagnosis of RTS.

Note

No disclaimers. Consent for publication of their details and photographs have been taken from the parents of both the children. There is no conflict of interest among all authors.


Author Contribution

S.Y. reviewed the literature and drafted the initial version of the manuscript. N.B. helped assess the dermatological manifestations. N.G. and S.T. helped in the acquisition of data. J.K. performed molecular testing. N.G., M.K., and S.T. contributed to literature review and critically revised the manuscript. All the authors contributed to drafting of the manuscript and approved the final version of the manuscript.


 
  • References

  • 1 Simon T, Kohlhase J, Wilhelm C, Kochanek M, De Carolis B, Berthold F. Multiple malignant diseases in a patient with Rothmund–Thomson syndrome with RECQL4 mutations: Case report and literature review. Am J Med Genet A 2010; 152A (06) 1575-1579
  • 2 Khadilkar V, Yadav S, Agrawal KK. , et al; Indian Academy of Pediatrics Growth Charts Committee. Revised IAP growth charts for height, weight and body mass index for 5- to 18-year-old Indian children. Indian Pediatr 2015; 52 (01) 47-55
  • 3 Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 2010; 26 (05) 589-595
  • 4 Meyer LR, Zweig AS, Hinrichs AS. , et al. The UCSC Genome Browser database: extensions and updates 2013. Nucleic Acids Res 2013; 41 (Database issue): D64-D69
  • 5 Kitao S, Lindor NM, Shiratori M, Furuichi Y, Shimamoto A. Rothmund-Thomson syndrome responsible gene, RECQL4: genomic structure and products. Genomics 1999; 61 (03) 268-276
  • 6 Borozdin W, Steinmann K, Albrecht B. , et al. Detection of heterozygous SALL1 deletions by quantitative real time PCR proves the contribution of a SALL1 dosage effect in the pathogenesis of Townes-Brocks syndrome. Hum Mutat 2006; 27 (02) 211-212
  • 7 Sangrithi MN, Bernal JA, Madine M. , et al. Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund–Thomson syndrome. Cell 2005; 121 (06) 887-898
  • 8 Petkovic M, Dietschy T, Freire R, Jiao R, Stagljar I. The human Rothmund-Thomson syndrome gene product, RECQL4, localizes to distinct nuclear foci that coincide with proteins involved in the maintenance of genome stability. J Cell Sci 2005; 118 (Pt. 18): 4261-4269
  • 9 Kääriäinen H, Ryöppy S, Norio R. RAPADILINO syndrome with radial and patellar aplasia/hypoplasia as main manifestations. Am J Med Genet 1989; 33 (03) 346-351
  • 10 Larizza L, Roversi G, Volpi L. Rothmund–Thomson syndrome. Orphanet J Rare Dis 2010; 5: 2
  • 11 Kumar P, Sharma PK, Gautam RK, Jain RK, Kar HK. Late-onset Rothmund–Thomson syndrome. Int J Dermatol 2007; 46 (05) 492-493
  • 12 Roinioti TD, Stefanopoulos PK. Short root anomaly associated with Rothmund-Thomson syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 103 (01) e19-e22
  • 13 Mehollin-Ray AR, Kozinetz CA, Schlesinger AE, Guillerman RP, Wang LL. Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status. AJR Am J Roentgenol 2008; 191 (02) W62-6
  • 14 Cao F, Lu L, Abrams SA. , et al. Generalized metabolic bone disease and fracture risk in Rothmund–Thomson syndrome. Hum Mol Genet 2017; 26 (16) 3046-3055
  • 15 Siitonen HA, Kopra O, Kääriäinen H. , et al. Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases. Hum Mol Genet 2003; 12 (21) 2837-2844
  • 16 Kitao S, Shimamoto A, Goto M. , et al. Mutations in RECQL4 cause a subset of cases of Rothmund–Thomson syndrome. Nat Genet 1999; 22 (01) 82-84
  • 17 Siitonen HA, Sotkasiira J, Biervliet M. , et al. The mutation spectrum in RECQL4 diseases. Eur J Hum Genet 2009; 17 (02) 151-158