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p. L18P : a novel IDUA mutation that causes a distinct attenuated phenotype in mucopolysaccharidosis type I patients
Author(s) -
Pasqualim G.,
Ribeiro M.G.,
da Fonseca G.G.G.,
Szlago M.,
Sche A.,
Lemes A.,
Rojas M.V.M.,
Matte U.,
Giugliani R.
Publication year - 2015
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12507
Subject(s) - medicine , mucopolysaccharidosis , mucopolysaccharidosis type i , mucopolysaccharidosis i , phenotype , mutation , disease , biology , genetics , gene , enzyme replacement therapy
Mucopolysaccharidosis type I is a rare autosomal recessive disorder caused by deficiency of α‐ l ‐iduronidase ( IDUA ) which leads to a wide spectrum of clinical severity. Here, we describe the case of four male patients who present the previously undescribed p. L18P mutation. Patient 1 (p. L18P /p. L18P ) presents, despite multiple joint contractures, an attenuated phenotype. Patient 2 (p. L18P /p. W402X ) was diagnosed at 4 years of age with bone dysplasia, coarse facies, limited mobility, claw hands and underwent bilateral carpal tunnel surgery at 6 years of age. Patients 3 and 4 (both p. L18P /p. L18P ) are brothers. Patient 3 was diagnosed at 4 years of age, when presented claw hands, lower limb and shoulder pain, restricted articular movement and bilateral carpal tunnel syndrome. Patient 4 was diagnosed at 17 months of age when presented lower limb pain at night, respiratory allergy and repeated upper airways infections. Bioinformatics analysis indicates that p. L18P mutation reduces the signal peptide to 25 amino acids and alters its secondary structure. In conclusion, we report a new IDUA variant that alters the structure of the signal peptide, which likely impairs transport to lysosomes. Moreover, it leads to a distinct attenuated phenotype with mainly bone and cartilage symptoms, without visceromegalies, heart disease, or cognitive impairment.