Further cases of “neighbor” mutations in mucopolysaccharidosis type II

Schwartz, Ida Vanessa Döederlein; Lima, Luciane Cauduro; Tylee, Karen; Sobrinho, Ruy P. Oliveira; Norato, Denise Yvonne Janovitz; Duarte, Andréa R.; Besley, G. T. N.; Burin, Maira G.; Matte, Úrsula; Giugliani, Roberto; Leistner-Segal, Sandra

doi:10.1002/ajmg.a.31317

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…The mother was a carrier of both mutations, but not the grandmother and the 4 maternal aunts. Few other reports described the presence of “neighbor” mutations [6]. The finding of these two close mutations in the patient and his mother but not in the grandmother suggests that they are de novo mutations in a mutation-prone region and reinforces the idea that they arose simultaneously.…”

Section: Resultssupporting

confidence: 56%

Identification of 17 novel mutations in 40 Argentinean unrelated families with mucopolysaccharidosis type II (Hunter syndrome)

Amartino

Ceci

Masllorens

et al. 2014

Molecular Genetics and Metabolism Reports

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Mucopolysaccharidosis type II (MPSII) is an X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulfatase (IDS). The human IDS gene is located in chromosome Xq28. This is the first report of genotype and phenotype characterization of 49 Hunter patients from 40 families of Argentina. Thirty different alleles have been identified, and 57% were novel. The frequency of de novo mutations was 10%. Overall, the percentage of private mutations in our series was 75%.

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Section: Resultssupporting

confidence: 56%

Identification of 17 novel mutations in 40 Argentinean unrelated families with mucopolysaccharidosis type II (Hunter syndrome)

Amartino

Ceci

Masllorens

et al. 2014

Molecular Genetics and Metabolism Reports

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“…We chose to discriminate the missense "neighbor" variants to better characterize this molecular finding since it has already been reported like this in the literature (Schwartz et al, 2006). There are five patients with missense "neighbor" variants in our cohort.…”

Section: Discussionmentioning

confidence: 99%

“…Four patients have a c.467C>A/c.463 T>C, and one patient have a c.1466G>A/c.1454 T>C. The "neighbor" mutations have been formerly described (Ricci et al, 2003;Schwartz et al, 2006;Timms, Huckett, Belmont, Shapira, & Gibbs, 1998) and are located in mutation-rich regions of the IDS gene (exons V, VIII, and IX) involving non-conserved codons.…”

Section: Discussionmentioning

confidence: 99%

“…We classified the IDS variant types in our cohort according to The Human Gene Mutation Database in single base-pair substitutions, which comprises missense, nonsense, and splicing; and in small/large gene alterations, which comprises small deletions (≤20 bp), small insertions/duplications (≤20 bp), small indels (≤20 bp), gross deletions (>20 bp), gross insertions/duplications (>20 bp), complex rearrangements, and regulatory (Stenson et al, 2017). When two point mutations were found in one patient, we classified the variant as "neighbor" (Ricci et al, 2003;Schwartz et al, 2006). We also report one single base-pair substitution that lead to the incorporation of the same amino acid as a "synonymous" variant, since there is increasing evidence that those variants can be disease causing (Zhou et al, 2012).…”

Section: Patients and Laboratorial Analysismentioning

confidence: 99%

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Genotype–phenotype studies in a large cohort of Brazilian patients with Hunter syndrome

Josahkian

Brusius-Facchin

Netto

et al. 2021

American J of Med Genetics Pt C

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“…After the identification of both mutations in the index case, they can be tested in the parents to confirm inheritance and rule out the presence of two “in cis” mutations, as has already been reported for other MPS. 46 It is also possible to analyze its presence in other family members for identification of carriers or other affected individuals, using several methodologies according to the lab expertise and equipment available. Simple methods such as restriction fragment length polymorphisms can be used for mutations which lay within an enzyme restriction site which allows the digestion of the PCR product with specific restriction enzymes.…”

Section: Mutation Identificationmentioning

confidence: 99%

Diagnostic and treatment strategies in mucopolysaccharidosis VI

Vairo¹,

Federhen²,

Baldo³

et al. 2015

TACG

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Mucopolysaccharidosis VI (MPS VI) is a very rare autosomal recessive disorder caused by mutations in the ARSB gene, which lead to deficient activity of the lysosomal enzyme ASB. This enzyme is important for the breakdown of the glycosaminoglycans (GAGs) dermatan sulfate and chondroitin sulfate, which accumulate in body tissues and organs of MPS VI patients. The storage of GAGs (especially dermatan sulfate) causes bone dysplasia, joint restriction, organomegaly, heart disease, and corneal clouding, among several other problems, and reduced life span. Despite the fact that most cases are severe, there is a spectrum of severity and some cases are so attenuated that diagnosis is made late in life. Although the analysis of urinary GAGs and/or the measurement of enzyme activity in dried blood spots are useful screening methods, the diagnosis is based in the demonstration of the enzyme deficiency in leucocytes or fibroblasts, and/or in the identification of pathogenic mutations in the ARSB gene. Specific treatment with enzyme replacement has been available since 2005. It is safe and effective, bringing measurable benefits and increased survival to patients. As several evidences indicate that early initiation of therapy may lead to a better outcome, newborn screening is being considered for this condition, and it is already in place in selected areas where the incidence of MPS VI is increased. However, as enzyme replacement therapy is not curative, associated therapies should be considered, and research on innovative therapies continues. The management of affected patients by a multidisciplinary team with experience in MPS diseases is highly recommended.

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Further cases of “neighbor” mutations in mucopolysaccharidosis type II

Cited by 5 publications

References 14 publications

Identification of 17 novel mutations in 40 Argentinean unrelated families with mucopolysaccharidosis type II (Hunter syndrome)

Identification of 17 novel mutations in 40 Argentinean unrelated families with mucopolysaccharidosis type II (Hunter syndrome)

Genotype–phenotype studies in a large cohort of Brazilian patients with Hunter syndrome

Diagnostic and treatment strategies in mucopolysaccharidosis VI

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