Abstract
Acromesomelic dysplasia, type Maroteaux is a disorder characterized by disproportionate short stature predominantly affecting the middle and distal segments of the upper and lower limbs. It is an autosomal recessive disorder due to mutation in NPR2 gene which impairs skeletal growth. To screen the mutations in the gene NPR2, all of its coding exons and splice junction sites were PCR amplified from genomic DNA of affected individuals of four families and sequenced. Four homozygous mutations in four different families were identified. These include three novel mutations including a deletion frameshift mutation (p.Cys586Ter), one nonsense mutation (p.Arg479Ter), one missense mutation (p.Val187Asp) and one reported missense mutation (p.Tyr338Cys). The study describes phenotypes of Indian patients and expands the mutation spectrum of the disorder.
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Amano N., Mukai T., Ito Y., Narumi S., Tanaka T., Yokoya S. et al. 2014 Identification and functional characterization of two novel NPR2 mutations in Japanese patients with short stature. J. Clin. Endocrinol. Metab. 99, E713–E718.
Bartels C. F., Bükülmez H., Padayatti P., Rhee D. K., van Ravenswaaij-Arts C., Pauli R. M. et al. 2004 Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal growth and cause acromesomelic dysplasia, type Maroteaux. Am. J. Hum. Genet. 75, 27–34.
Borrelli P., Fasanelli S. and Marini R. 1983 Acromesomelic dwarfism in a child with an interesting family history. Pediatr. Radiol. 13, 165–168.
Hisado-Oliva A., Garre-Vázquez A. I., Santaolalla-Caballero F., Belinchón A., Barreda-Bonis A. C., Vasques G. A. et al. 2015 Heterozygous NPR2 mutations cause disproportionate short stature, similar to Léri–Weill dyschondrosteosis. J. Clin. Endocrinol. Metab. 100, E1133–E1142.
Irfanullah U. M., Khan S. and Ahmad W. 2015 Homozygous sequence variants in the NPR2 gene underlying acromesomelic dysplasia Maroteaux type (AMDM) in consanguineous families. Ann. Hum. Genet. 79, 238–244.
Kant S. G., Polinkovsky A., Mundlos S., Zabel B., Thomeer R. T., Zonderland H. M. et al. 1998 Acromesomelic dysplasia Maroteaux type maps to human chromosome 9. Am. J. Hum. Genet. 63, 155–162.
Khan S., Ali R. H., Abbasi S., Nawaz M., Muhammad N. and Ahmad W. 2012 Novel mutations in natriuretic peptide receptor-2 gene underlie acromesomelic dysplasia, type Maroteaux. BMC Med. Genet. 13, 44.
Langer L. O. and Garrett R. T. 1980 Acromesomelic dysplasia. Radiology 137, 349–355.
Miura K., Kim O. H., Lee H. R., Namba N., Michigami T., Yoo W. J. et al. 2014 Overgrowth syndrome associated with a gain-of-function mutation of the natriuretic peptide receptor 2 (NPR2) gene. Am. J. Med. Genet. A 164A, 156–163.
Olney R. C., Bükülmez H., Bartels C. F., Prickett T. C., Espiner E. A., Potter L. R. et al. 2006 Heterozygous mutations in natriuretic peptide receptor-B (NPR2) are associated with short stature. J. Clin. Endocrinol. Metab. 91, 1229–1232.
Tamura N., Ogawa Y., Chusho H., Nakamura K., Nakao K., Suda M. et al. 2000 Cardiac fibrosis in mice lacking brain natriuretic peptide. Proc. Natl. Acad. Sci. USA 97, 4239–4344.
Vasques G. A., Amano N., Docko A. J., Funari M. F., Quedas E. P., Nishi M. Y. et al. 2013 Heterozygous mutations in natriuretic peptide receptor-B (NPR2) gene as a cause of short stature in patients initially classified as idiopathic short stature. J. Clin. Endocrinol. Metab. 98, E1636–E1644.
Wang S. R., Jacobsen C. M., Carmichael H., Edmund A. B., Robinson J. W., Olney R. C. et al. 2015 Heterozygous mutations in natriuretic peptide receptor-B (NPR2) gene as a cause of short stature. Hum. Mutat. 36, 474–481.
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We sincerely thank the cooperation of patient’s families and acknowledge the Indian Council of Medical Research, New Delhi, for funding (BMS-63/8/2010).
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Corresponding editor: S. Ganesh
[Srivastava P., Tuteja M., Dalal A., Mandal K. and Phadke S. R. 2016 Novel mutations in the transmembrane natriuretic peptide receptor NPR-B gene in four Indian families with acromesomelic dysplasia, type Maroteaux. J. Genet. 95, xx–xx]
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SRIVASTAVA, P., TUTEJA, M., DALAL, A. et al. Novel mutations in the transmembrane natriuretic peptide receptor NPR-B gene in four Indian families with acromesomelic dysplasia, type Maroteaux. J Genet 95, 905–909 (2016). https://doi.org/10.1007/s12041-016-0715-1
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DOI: https://doi.org/10.1007/s12041-016-0715-1