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Genotype–phenotype studies in a large cohort of Brazilian patients with Hunter syndrome
Author(s) -
Josahkian Juliana Alves,
BrusiusFacchin Ana Carolina,
Netto Alice Brinckmann Oliveira,
LeistnerSegal Sandra,
Málaga Diana Rojas,
Burin Maira Graeff,
MichelinTirelli Kristiane,
Trapp Franciele Barbosa,
CardosodosSantos Augusto César,
Ribeiro Erlane Marques,
Kim Chong Ae,
Siqueira Ana Cecília Menezes,
Santos Mara Lucia,
Valle Daniel Almeida,
Silva Raquel Tavares Boy,
Horovitz Dafne Dain Gandelman,
Medeiros Paula Frassinetti Vasconcelos,
Souza Carolina Fischinger Moura,
Giuliani Liane de Rosso,
Miguel Diego Santana Chaves Geraldo,
SantanadaSilva Luiz Carlos,
Galera Marcial Francis,
Giugliani Roberto
Publication year - 2021
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.31915
Subject(s) - genotype , hunter syndrome , missense mutation , phenotype , mucopolysaccharidosis type ii , allele , genetics , disease , genotype phenotype distinction , genotyping , cohort , enzyme replacement therapy , genetic heterogeneity , lysosomal storage disease , biology , gene , medicine
Mucopolysaccharidosis type II (MPS II) is an X‐linked inherited disease caused by pathogenic variants in the IDS gene, leading to deficiency of the lysosomal enzyme iduronate‐2‐sulfatase and consequent widespread storage of glycosaminoglycans, leading to several clinical consequences, with progressive manifestations which most times includes cognitive decline. MPS II has wide allelic and clinical heterogeneity and a complex genotype–phenotype correlation. We evaluated data from 501 Brazilian patients diagnosed with MPS II from 1982 to 2020. We genotyped 280 of these patients (55.9%), which were assigned to 206 different families. Point mutations were present in 70% of our patients, being missense variants the most frequent. We correlated the IDS pathogenic variants identified with the phenotype (neuronophatic or non‐neuronopathic). Except for two half‐brothers, there was no discordance in the genotype–phenotype correlation among family members, nor among MPS II patients from different families with the same single base‐pair substitution variant. Mothers were carriers in 82.0% of the cases. This comprehensive study of the molecular profile of the MPS II cases in Brazil sheds light on the genotype–phenotype correlation and helps the better understanding of the disease and the prediction of its clinical course, enabling the provision of a more refined genetic counseling to the affected families.