Mucopolysaccharidosis type II: Identification of six novel mutations in Italian patients

Villani, Guido; Balzano, Nicola; Grosso, Michela; Salvatore, Francesco; Izzo, Paola; Natale, Paola Di

doi:10.1002/(sici)1098-1004(1997)10:1<71::aid-humu10>3.0.co;2-x

Cited by 17 publications

(2 citation statements)

References 20 publications

(22 reference statements)

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“…The other aminoacid exchange, p.His335Arg, led to MPS II phenotype . At position p.Lys347 four other exchanges (p.Lys347Gln, p.Lys347Thr, Lys347Ile, p.Lys347Glu) were described in patients with MPS II .…”

Section: Resultsmentioning

confidence: 99%

Genotype–phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis typeII

et al. 2017

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Mucopolysaccharidosis type II (Hunter syndrome, MPS II, OMIM 309900) is an X-linked lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase (IDS). We analyzed clinical and laboratory data from 44 Slavic patients with this disease. In total, 21 Czech, 7 Slovak, 9 Croatian and 7 Serbian patients (43 M/1 F) were included in the study (median age 11.0 years, range 1.2-43 years). Birth prevalence ranged from 1:69,223 (Serbia) to 1:192,626 (Czech Rep.). In the majority of patients (71%), the disease manifested in infancy. Cognitive functions were normal in 10 patients. Four, six and 24 patients had mild, moderate, and severe developmental delay, respectively, typically subsequent to developmental regression (59%). Residual enzyme activity showed no predictive value, and estimation of glycosaminoglycans (GAGs) had only limited importance for prognosis. Mutation analysis performed in 36 families led to the identification of 12 novel mutations, eight of which were small deletions/insertions. Large deletions/rearrangements and all but one small deletion/insertion led to a severe phenotype. This genotype-phenotype correlation was also identified in six cases with recurrent missense mutations. Based on patient genotype, the severity of the disease may be predicted with high probability in approximately half of MPS II patients.

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Section: Resultsmentioning

confidence: 99%

Genotype–phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis typeII

et al. 2017

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“…(Pro467Leu)Severe (P24)Phenotype not reported [22]c.1403G>Ap. (Arg468Gln)Severe (P20)Severe [71]; severe [57]; severe [67]; four severe patients [63]; severe [34]; three severe patients [35]; severe [31]; severe [25]; severe [18]c.1478G>Cp. (Arg493Pro)Severe (P17)Phenotype not reported [46]SGSHc.197C>Gp.…”

Section: Resultsmentioning

confidence: 99%

Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study

et al. 2019

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Mucopolysaccharidoses (MPS) are a subgroup of 11 monogenic lysosomal storage disorders due to the deficit of activity of the lysosomal hydrolases deputed to the degradation of mucopolysaccharides. Although individually rare, all together they account for at least 1:25,000 live births. In this study, we present the genetic analysis of a population of 71 MPS patients enrolled in a multicenter Italian study. We re-annotated all variants, according to the latest recommendations, and re-classified them as suggested by the American College of Medical Genetics and Genomics. Variant distribution per type was mainly represented by missense mutations. Overall, 10 patients had received no molecular diagnosis, although 6 of them had undergone either HSCT or ERT, based on clinical and enzymatic evaluations. Moreover, nine novel variants are reported. Conclusions : Our analysis underlines the need to complete the molecular diagnosis in patients previously diagnosed only on a biochemical basis, suggests a periodical re-annotation of the variants and solicits their deposition in public databases freely available to clinicians and researchers. We strongly recommend a molecular diagnosis based on the analysis of the “trio” instead of the sole proband. These recommendations will help to obtain a complete and correct diagnosis of mucopolysaccharidosis, rendering also possible genetic counseling. What is known • MPS are a group of 11 metabolic genetic disorders due to deficits of enzymes involved in the mucopolysaccharides degradation. • Molecular analysis is commonly performed to confirm enzymatic assays. What is new • Eighty-six percent of the 71 patients we collected received a molecular diagnosis; among them, 9 novel variants were reported. • We stress the importance of molecular diagnosis in biochemically diagnosed patients, encourage a periodical re-annotation of variants according to the recent nomenclature and their publication in open databases. Electronic supplementary material The online version of this article (10.1007/s00431-019-03341-8) contains supplementary material, which is available to authorized users.

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Mutation analysis of iduronate-2-sulphatase gene in 24 patients with Hunter syndrome: Characterisation of 6 novel mutations

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Mucopolysaccharidosis type II: Identification of six novel mutations in Italian patients

Cited by 17 publications

References 20 publications

Genotype–phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis typeII

Genotype–phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis typeII

Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study

Mutation analysis of iduronate-2-sulphatase gene in 24 patients with Hunter syndrome: Characterisation of 6 novel mutations

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