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GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report.
BMC Med Genet. 2018 09 12; 19(1):162.BM

Abstract

BACKGROUND

Mucolipidosis alpha/beta is an inborn error of metabolism characterized by deficiency of GlcNAc-1-phosphotransferase, in which essential alpha/beta subunits are encoded by the GNPTAB gene. The autosomal recessive condition is due to disruptions of hydrolase mannose 6-phosphate marker generation, defective lysosomal targeting and subsequent intracellular accumulation of non-degraded material. Clinical severity depends on residual GlcNAc-1-phosphotransferase activity, which distinguishes between the milder type III disease and the severe, neonatal onset type II disease.

CASE PRESENTATION

We report the clinical, biochemical and genetic diagnosis of mucolipidosis III alpha/beta in a two-year-old Chinese boy who initially presented with poor weight gain, microcephaly and increased tone. He was confirmed to harbor the common splice site mutation c.2715 + 1G > A and the nonsense variant c.2404C > T (p.Q802*). Clinically, the patient had multiple phenotypic features typical of mucopolysaccharidosis including joint contractures, coarse facial features, kypho-lordosis, pectus carinatum and umbilical hernia. However, the relatively mild developmental delay compared to severe type I and type II mucopolysaccharidosis and the absence of macrocephaly raised the possibility of the less commonly diagnosed mucolipidosis alpha/beta. Critical roles of lysosomal enzyme activity assay, which showed elevated α-iduronidase, iduronate sulfatase, galactose-6-sulphate sulphatase, arylsulfatase B and α-hexosaminidase activities; and genetic study, which confirmed the parental origin of both mutations, were highlighted.

CONCLUSIONS

The recently reported nonsense variant c.2404C > T in the GNPTAB gene is further recognized and this contributes to the genotype-phenotype spectrum of mucolipidosis alpha/beta.

Authors+Show Affiliations

Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Special Administrative Region, China.Department of Paediatrics & Adolescent Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Special Administrative Region, China.Department of Paediatrics & Adolescent Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Special Administrative Region, China.Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Special Administrative Region, China. poonwt@ha.org.hk.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30208878

Citation

Ho, Chi-Chun, et al. "GNPTAB c.2404C > T Nonsense Mutation in a Patient With Mucolipidosis III Alpha/beta: a Case Report." BMC Medical Genetics, vol. 19, no. 1, 2018, p. 162.
Ho CC, Tsung LL, Liu KT, et al. GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report. BMC Med Genet. 2018;19(1):162.
Ho, C. C., Tsung, L. L., Liu, K. T., & Poon, W. T. (2018). GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report. BMC Medical Genetics, 19(1), 162. https://doi.org/10.1186/s12881-018-0679-5
Ho CC, et al. GNPTAB c.2404C > T Nonsense Mutation in a Patient With Mucolipidosis III Alpha/beta: a Case Report. BMC Med Genet. 2018 09 12;19(1):162. PubMed PMID: 30208878.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report. AU - Ho,Chi-Chun, AU - Tsung,Lilian Li-Yan, AU - Liu,Kam-Tim, AU - Poon,Wing-Tat, Y1 - 2018/09/12/ PY - 2018/05/31/received PY - 2018/09/03/accepted PY - 2018/9/14/entrez PY - 2018/9/14/pubmed PY - 2019/5/24/medline KW - GNPTAB KW - GlcNAc-1-phosphotransferase KW - Mucolipidosis III alpha/beta KW - Nonsense variant KW - P.Q802* KW - Pseudo-hurler polydystrophy SP - 162 EP - 162 JF - BMC medical genetics JO - BMC Med. Genet. VL - 19 IS - 1 N2 - BACKGROUND: Mucolipidosis alpha/beta is an inborn error of metabolism characterized by deficiency of GlcNAc-1-phosphotransferase, in which essential alpha/beta subunits are encoded by the GNPTAB gene. The autosomal recessive condition is due to disruptions of hydrolase mannose 6-phosphate marker generation, defective lysosomal targeting and subsequent intracellular accumulation of non-degraded material. Clinical severity depends on residual GlcNAc-1-phosphotransferase activity, which distinguishes between the milder type III disease and the severe, neonatal onset type II disease. CASE PRESENTATION: We report the clinical, biochemical and genetic diagnosis of mucolipidosis III alpha/beta in a two-year-old Chinese boy who initially presented with poor weight gain, microcephaly and increased tone. He was confirmed to harbor the common splice site mutation c.2715 + 1G > A and the nonsense variant c.2404C > T (p.Q802*). Clinically, the patient had multiple phenotypic features typical of mucopolysaccharidosis including joint contractures, coarse facial features, kypho-lordosis, pectus carinatum and umbilical hernia. However, the relatively mild developmental delay compared to severe type I and type II mucopolysaccharidosis and the absence of macrocephaly raised the possibility of the less commonly diagnosed mucolipidosis alpha/beta. Critical roles of lysosomal enzyme activity assay, which showed elevated α-iduronidase, iduronate sulfatase, galactose-6-sulphate sulphatase, arylsulfatase B and α-hexosaminidase activities; and genetic study, which confirmed the parental origin of both mutations, were highlighted. CONCLUSIONS: The recently reported nonsense variant c.2404C > T in the GNPTAB gene is further recognized and this contributes to the genotype-phenotype spectrum of mucolipidosis alpha/beta. SN - 1471-2350 UR - https://www.unboundmedicine.com/medline/citation/30208878/GNPTAB_c.2404C_>_T_nonsense_mutation_in_a_patient_with_mucolipidosis_III_alpha/beta:_a_case_report L2 - https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-018-0679-5 DB - PRIME DP - Unbound Medicine ER -