β-Mannosidosis caused by a novel homozygous intragenic inverted duplication in MANBA .

Autor:	Blomqvist M; Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg 413 45, Sweden.; Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg 413 45, Sweden., Smeland MF; Department of Medical Genetics, Division of Child and Adolescent Health, University Hospital of North Norway, Tromsø 9038, Norway., Lindgren J; Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg 413 45, Sweden., Sikora P; Laboratory Medicine, Sahlgrenska University Hospital, Gothenburg 413 45, Sweden.; Clinical Genomics Gothenburg, Science for Life Laboratories, Gothenburg 405 30, Sweden., Riise Stensland HMF; Department of Medical Genetics, Division of Child and Adolescent Health, University Hospital of North Norway, Tromsø 9038, Norway., Asin-Cayuela J; Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg 413 45, Sweden.; Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg 413 45, Sweden.
Jazyk:	angličtina
Zdroj:	Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2019 Jun 03; Vol. 5 (3). Date of Electronic Publication: 2019 Jun 03 (Print Publication: 2019).
DOI:	10.1101/mcs.a003954
Abstrakt:	β-Mannosidosis is a lysosomal storage disorder characterized by accumulation of disaccharides due to deficiency of the lysosomal enzyme β-mannosidase. The disease is caused by mutations in MANBA and is extremely rare in humans. Although the clinical presentation is heterogeneous, common symptoms include various degrees of developmental delay, behavioral disturbances, hearing loss, and frequent infections. We report a 15-yr-old girl presenting with mild intellectual disability, sensorineural hearing loss, severe behavioral disturbances, dysmorphic traits, and evolving angiokeratomas. Copy-number variation analysis of next-generation sequencing (NGS) data indicated increased coverage in exons 8-11 of MANBA Low β-mannosidase activity (1 µkatal/kg protein, refv 25-40) established the diagnosis of β-mannosidosis. Whole-genome sequencing (WGS) and cDNA analysis revealed a novel homozygous intragenic inverted duplication in MANBA, where a 13.1-kb region between introns 7 and 11 was duplicated and inserted in an inverted orientation, creating a 67-base nonduplicated gap at the insertion point. Both junctions showed microhomology regions. The inverted duplication resulted in exon skipping of exons 8-9 or 8-10. Our report highlights the importance of copy-number variation analysis of data from NGS and in particular the power of WGS in the identification and characterization of copy-number variants. (© 2019 Blomqvist et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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