ß-Mannosidosis caused by a novel homozygous intragenic inverted duplication in MANBA.
Cold Spring Harb Mol Case Stud
; 5(3)2019 06.
Article
en En
| MEDLINE
| ID: mdl-30886116
ABSTRACT
ß-Mannosidosis is a lysosomal storage disorder characterized by accumulation of disaccharides due to deficiency of the lysosomal enzyme ß-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 ß-mannosidase activity (1 µkatal/kg protein, refv 25-40) established the diagnosis of ß-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.
Palabras clave
abnormality of the vasculature of the conjunctiva; aggressive behavior; alacrima; angiokeratoma corporis diffusum; attention-deficit hyperactivity disorder; bilateral sensorineural hearing impairment; broad nasal tip; chronic constipation; hypohidrosis/hyperhidrosis; impulsivity; increased urinary disaccharide excretion; intellectual disability, mild; sleep disturbance; thin upper lip vermilion; upslanted palpebral fissure; wide nasal ridge
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Beta-Manosidosis
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Variaciones en el Número de Copia de ADN
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Angioqueratoma
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Manosidasas
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Adolescent
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Female
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Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article