Molecular analysis of mucopolysaccharidosis type VI in Iranian patients; the influence of founder effect and consanguinity.

Background: Mucopolysaccharidosis type VI (MPS VI), also known as Manteaux-Lamy syndrome, is an autosomal recessive lysosomal storage disorder caused by deficiency of the enzyme arylsulfatase B(ARSB). This syndrome is progressive and affects many tissues and organs, leading to inflammation and scarring. The classic clinical features of Maroteaux-Lamy syndrome are significant impairment of the osteoarticular system with dysostosis multiplex, short stature and motor dysfunction. The rate at which symptoms appear and worsen can vary between affected individuals. Mutations in the ARSB gene are responsible for MPS VI. We investigated the clinical presentation and molecular basis of patients with MPS VI for the first time in Yazd province, Iran.

Methods: Of the 52 people who took part in this project, there were 13 probands. Whole exome sequencing (WES) was performed in 2 of them and the nominated mutation in the ARSB (c.430G > A) was verified by Sanger sequencing in the remaining patients.

Results: All patients had parental consanguinity, except for one family in which the parents were unrelated. All patients were of Fars ethnicity and had characteristic phenotypes such as severe short stature, cardiac involvement, coarse facial features, and corneal opacities. Sequence analysis of the ARSB gene revealed a pathogenic homozygous missense mutation c.430G > A (p. Gly144Arg) in all patients. This type of mutation influenced the phenotypes of the severe patients.

Conclusions: These results expand the genetic databases of Iranian patients with MPS VI and would be very helpful for the high-risk families to accelerate the detection of carriers and to perform prenatal testing for the disorder in this population in a cost-effective manner. There is a possibility that other unknown mutations are responsible for the disease. The decision to screen for and detect carriers of this disease at a national level is awaited. The results of the present study could be an asset for married families in part of the city of Meybod. The results offer a way for early detection of patients and carriers of the disease.