Genotype–phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis type<scp>II</scp>

Dvořáková, Lenka; Vlášková, Hana; Sarajlija, Adrijan; Ramadža, Danijela Petković; Poupětová, Helena; Hrubá, Eva; Hlavatá, Anna; Bzdúch, Vladimír; Pešková, Karolína; Štorkánová, Gabriela; Kecman, Bozica; Djordjevic, Maja; Barić, Ivo; Fumić, Ksenija; Barišić, Ingeborg; Řeboun, Martin; Kulhánek, Jan; Zeman, Jiří; Magner, Martin

doi:10.1111/cge.12927

Cited by 28 publications

(21 citation statements)

References 26 publications

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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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Section: Resultsmentioning

confidence: 99%

Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study

et al. 2019

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“…As a consequence, genotype-phenotype correlations are difficult to investigate for most types of variants, although, as Hunter syndrome is an X-linked trait, each patient phenotype is due to the expression of a single variant. Only large deletions/insertions, complex rearrangements, and nonsense and splicing variants are commonly associated with severe forms [45,46].…”

Section: Type Of Variants Frequency (%)mentioning

confidence: 99%

“…Most Hunter patients present no residual IDS activity [68], whilst some attenuated patients have been reported to have 0.2%-2.4% of a healthy control's activity [69]. A recent paper reported no correlation between residual IDS activity and patients' phenotypes, and just one patient with an attenuated form showed a residual activity of 14.6% [45]. Molecular genetic testing allows the identification of the disease-causing genetic variant, hence confirming the results of the biochemical evaluations.…”

Section: Diagnosismentioning

confidence: 99%

Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment

D’Avanzo

Rigon

Zanetti

et al. 2020

IJMS

107

145

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Mucopolysaccharidosis type II (MPS II, Hunter syndrome) was first described by Dr. Charles Hunter in 1917. Since then, about one hundred years have passed and Hunter syndrome, although at first neglected for a few decades and afterwards mistaken for a long time for the similar disorder Hurler syndrome, has been clearly distinguished as a specific disease since 1978, when the distinct genetic causes of the two disorders were finally identified. MPS II is a rare genetic disorder, recently described as presenting an incidence rate ranging from 0.38 to 1.09 per 100,000 live male births, and it is the only X-linked-inherited mucopolysaccharidosis. The complex disease is due to a deficit of the lysosomal hydrolase iduronate 2-sulphatase, which is a crucial enzyme in the stepwise degradation of heparan and dermatan sulphate. This contributes to a heavy clinical phenotype involving most organ-systems, including the brain, in at least two-thirds of cases. In this review, we will summarize the history of the disease during this century through clinical and laboratory evaluations that allowed its definition, its correct diagnosis, a partial comprehension of its pathogenesis, and the proposition of therapeutic protocols. We will also highlight the main open issues related to the possible inclusion of MPS II in newborn screenings, the comprehension of brain pathogenesis, and treatment of the neurological compartment.

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“…IDS activity was significantly diminished in all patients in whom enzyme analysis was performed. Residual enzyme activity showed no predictive value (31).…”

Section: Discussionmentioning

confidence: 94%

Clinical, Biochemical and Molecular Characteristics of Fifteen Patients with Mucopolysaccharidosis Type II in Western Turkey

Yazici¹,

Canda²,

Er³

et al. 2018

jpr

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Mucopolysaccharidosis Type II (MPS II, Hunter syndrome, OMIM 309900) is a rare X-linked lysosomal storage disease due to a deficiency of the iduronate-2-sulfatase (IDS) enzyme, which is one of the degradative enzymes of mucopolysaccharides. The purpose of this study is to present the clinical, biochemical and molecular characteristics of fifteen patients with MPS II in western Turkey. Materials and Methods: A retrospective study was carried out on fifteen patients with MPS II who were followed up by Ege University Faculty of Medicine, Unit of Pediatric Metabolic Diseases and Nutrition between October 2004 and September 2017. Results: The age range of the patients enrolled in the study was between 11 months and 318 months at the time of diagnosis. The most common symptom was coarse face. On physical examination, all of the patients presented with coarse face, macrocephaly and organomegaly. Except for one patient, all other were severe phenotype. IDS activity was significantly decreased in all patients in whom enzyme analysis was performed. In this study, one novel mutation was described. Conclusion: This is the first study on the clinical and molecular characterization of Turkish MPS II patients. The majority of the patients had neurologic involvement with different degrees of severity. The molecular analysis revealed one novel mutation.

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

Cited by 28 publications

References 26 publications

Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study

Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study

Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment

Clinical, Biochemical and Molecular Characteristics of Fifteen Patients with Mucopolysaccharidosis Type II in Western Turkey

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