Clinical and mutation profile of multicentric osteolysis nodulosis and arthropathy

Gandham SriLakshmi Bhavani; Hitesh Shah; Anju Shukla; Neerja Gupta; Kalpana Gowrishankar; Anand P Rao; Madhulika Kabra; Meenal Agarwal; Prajnya Ranganath; Alka V Ekbote; Shubha R Phadke; Asha Kamath; Ashwin Dalal; Katta Mohan Girisha

doi:10.1002/ajmg.a.37447

Clinical and mutation profile of multicentric osteolysis nodulosis and arthropathy

Am J Med Genet A. 2016 Feb;170A(2):410-417. doi: 10.1002/ajmg.a.37447. Epub 2015 Nov 24.

Authors

Affiliations

¹ Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.
² Department of Orthopedics, Pediatric Orthopedics services, Kasturba Medical College, Manipal University, Manipal, India.
³ Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
⁴ Department of Medical Genetics, Kanchi Kamakoti Childs Trust Hospital, Chennai, Tamilnadu, India.
⁵ Manipal Hospital, Bangalore, India.
⁶ Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
⁷ Department of Medical Genetics, Nizam's Institute of Medical Sciences, Hyderabad, India.
⁸ Division of Diagnostics, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
⁹ Department of Clinical Genetics, Christian Medical College and Hospital, Vellore, India.
¹⁰ Department of Community Medicine, Kasturba Medical College, Manipal University, Manipal, Karnataka, India.

PMID: 26601801
DOI: 10.1002/ajmg.a.37447

Abstract

Multicentric osteolysis nodulosis and arthropathy (MONA) is an infrequently described autosomal recessive skeletal dysplasia characterized by progressive osteolysis and arthropathy. Inactivating mutations in MMP2, encoding matrix metalloproteinase-2, are known to cause this disorder. Fifteen families with mutations in MMP2 have been reported in literature. In this study we screened thirteen individuals from eleven families for MMP2 mutations and identified eight mutations (five novel and three known variants). We characterize the clinical, radiographic and molecular findings in all individuals with molecularly proven MONA from the present cohort and previous reports, and provide a comprehensive review of the MMP2 related disorders.

Keywords: MMP2; Torg-Winchester syndrome; multicentric osteolysis nodulosis and arthropathy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Amino Acid Sequence
Child
Child, Preschool
Cohort Studies
Female
Homozygote
Humans
Infant
Infant, Newborn
Male
Matrix Metalloproteinase 2 / genetics*
Molecular Sequence Data
Mutation / genetics*
Osteolysis / enzymology
Osteolysis / genetics*
Osteolysis / pathology
Prognosis
Sequence Homology, Amino Acid

Substances

MMP2 protein, human
Matrix Metalloproteinase 2

Supplementary concepts

Osteolysis hereditary multicentric