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Further defining the clinical and molecular spectrum of acromesomelic dysplasia type maroteaux: a Turkish tertiary center experience

Journal of Human Genetics volume 66, pages 585–596 (2021)Cite this article

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Abstract

Acromesomelic dysplasia type Maroteaux (AMDM, OMIM #602875) is an autosomal recessive disorder characterized by severe short stature, shortened middle and distal segments of the limbs, redundant skin of fingers, radial head subluxation or dislocation, large great toes and cranium, and normal intelligence. Only the skeletal system appears to be consistently affected. AMDM is caused by biallelic loss-of-function variants in the natriuretic peptide receptor B (NPRB or NPR2, OMIM #108961) which is involved in endochondral ossification and longitudinal growth of limbs and vertebrae. In this study, we investigated 26 AMDM patients from 22 unrelated families and revealed their genetic etiology in 20 families, via Sanger sequencing or exome sequencing. A total of 22 distinct variants in NPR2 (14 missense, 5 nonsense, 2 intronic, and 1 one-amino acid deletion) were detected, among which 15 were novel. They were in homozygous states in 19 patients and in compound heterozygous states in four patients. Parents with heterozygous NPR2 variants were significantly shorter than the control. Extra-skeletal abnormalities, including global developmental delay/intellectual disability, nephrolithiasis, renal cyst, and oligodontia were noted in the patient cohort. The high parental consanguinity rate might have contributed to these findings, probably associated with other gene variants. This study represents the largest cohort of AMDM from Turkey and regional countries and further expands the molecular and clinical spectrum of AMDM.

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Acknowledgements

We thank our patients and their families for their collaboration and participation. We also thank Ebru Bulut for DNA sequencing, sample handling and excellent technical assistance. The study was supported by Hacettepe University Research Projects Management System with Project ID: 14392.

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Authors and Affiliations

  1. Department of Pediatric Genetics, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Pelin Ozlem Simsek-Kiper, Gizem Urel-Demir, Gulen Eda Utine & Koray Boduroglu

  2. Department of Medical Genetics, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Ekim Z. Taskiran & Koray Boduroglu

  3. Institute of Public Health, Hacettepe University, Ankara, Turkey

    Umut Ece Arslan

  4. Department of Pediatric Genetics, Akdeniz University Faculty of Medicine, Antalya, Turkey

    Banu Nur & Ercan Mihci

  5. Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Mithat Haliloglu

  6. Department of Pediatric Genetics, Acibadem Mehmet Aydınlar University Faculty of Medicine, Istanbul, Turkey

    Yasemin Alanay

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  1. Pelin Ozlem Simsek-Kiper
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Correspondence to Pelin Ozlem Simsek-Kiper.

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Simsek-Kiper, P.O., Urel-Demir, G., Taskiran, E.Z. et al. Further defining the clinical and molecular spectrum of acromesomelic dysplasia type maroteaux: a Turkish tertiary center experience. J Hum Genet 66, 585–596 (2021). https://doi.org/10.1038/s10038-020-00871-0

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