Clinical and molecular characteristics of colombian patients with mucopolysaccharidosis IVA, and description of a new galns gene mutation

Abstract

A study published in 2012 estimated incidence of MPS IVA, in 0.68 cases per 100, 000 live births in Colombia, and according to the Colombian Fund for High-Cost Diseases, in 2014 there were 15 people diagnosed with MPS IV. To enhance the knowledge of the disease in the country, we aimed to characterize clinical and molecular findings in 12 MPS IVA patients. Twelve patients were included in the study, with most patients of female gender (n = 7, 58,3%), age range 2 to 28 years, average weight 26 kg (17.6–43 kg), average height 97 cm (92–104 cm), average BMI 27.6 kg/m2 (19.92–47.65 kg/m2). Clinical findings were similar to those described in the literature. GALNS gene molecular analysis showed five homozygous missense mutations in exon 11 c.1156C > T or p.R386C, a single nonsense mutation in the heterozygous state c.974G > A p.W325, and heterozygous in exon 9 mutation of exon 3 c.280C > T p.R94C, missense variant reported by Ogawa in 1995 [17]. There was only one patient that presented a homozygous missense mutation in exon 9 c.901G > T p.G301C and four patients showed the heterozygous form. A heterozygous missense mutation in exon 5 c.425A > T p.H142L, which has not been previously reported, was found in a female patient, 2 years 11 months of age. The diagnosis algorithms that include molecular analysis, bioinformatic predictive tools, pharmacogenomics, and proteomics helps to improve the diagnosis, treatment, and prognosis of patients affected by MPS IVA.

Identification of Missense Mutation Pro77Arg As A Founder Mutation in Morquio-A Syndrome in Indian Gujarati Patel Ethnicity

“…The GALNS enzyme activity in the KS positive patients ranged from undetectable to less than 10% of the total enzyme activity. Our results are consistent with that observed by Leong et al (12) in the Malaysian population and other reported studies (15,26,27).…”

Clinical outcomes in elderly patients with Morquio a syndrome receiving enzyme replacement therapy - experience in a Colombian center

“…In a study conducted in 2018 in the Colombian population, the pathogenic p.Gly301Cys variant was reported in 51.6% of the alleles analyzed. [ 14 , 15 ] These results are consistent with a previous description in 1997, with a reported prevalence of 68.4% for the p.G301C mutation, considered as a founder mutation in the Colombian population [ 16 ]. At present, this mutation has also been reported in the Moroccan, Portuguese, French, Brazilian and Spanish populations, being more frequent in the latter (20%).…”

“…This wide allelic heterogeneity in GALNS mutations is what supports the broad spectrum of clinical phenotypes observed in patients with MPS IVA. A genotype-phenotype correlation has been reported in some groups of patients, [ 11 , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] ] making it even more important to insist on early diagnosis followed by prompt initiation of treatment, in order to improve prognosis.…”

Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome): A review and classification of GALNS gene variants and reporting of 68 novel variants

“…In agreement with this, in the present update, 89.2% of all c.1023C>G alleles were reported in Brazil. Variant c.901G>T [p.(Gly301Cys)] was the next most represented allele in Brazil (13.3% of all Brazilian alleles) and also accounted for 46.6% and 12.4% of alleles reported in Colombia and Canada, respectively (Moisan et al, 2020 ; Moreno Giraldo et al, 2018 ; Tapiero‐Rodriguez et al, 2018 ).…”