Are we missing complex rearrangements by next generation diagnostic approaches: A case report of a complex rearrangement in MPS II
| Autor: | Francyne Kubaski, Maria L. Castro Moreira, Catarina Pereira, Roberto Giugliani, Rodolfo Bareiro |
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| Rok vydání: | 2019 |
| Předmět: |
Proband
Sanger sequencing Pediatrics medicine.medical_specialty Coarse facial features business.industry Endocrinology Diabetes and Metabolism Hepatosplenomegaly Gene mutation Biochemistry Short stature symbols.namesake Endocrinology Genetics medicine symbols Multiplex ligation-dependent probe amplification medicine.symptom Mucopolysaccharidosis type II business Molecular Biology |
| Zdroj: | Molecular Genetics and Metabolism. 126:S102 |
| ISSN: | 1096-7192 |
| DOI: | 10.1016/j.ymgme.2018.12.256 |
| Popis: | Mucopolysaccharidosis type II (MPS II) is caused by deficiency of Iduronate-2-sulfatase (IDS) that leads to accumulation of undegraded glycosaminoglycans. So far, over 630 mutations have been described for the IDS gene in the Human Gene mutation database and only 2% of these are classified as complex rearrangements. Here, we present the molecular diagnosis odyssey of an MPS II patient. Non-consanguineos parents had 3 children, the first daughter died with 2.6 years with no confirmed diagnosis but dysmorphic features, the second was a stillbirth with facial dysmorphic features at birth and the third son (proband) died with 6.1 years. He started walking with 2 years of age and had severly impaired speech development limited to few words. He started developing seizures at 4 years of age. Clinical examination revealed: short stature, coarse facial features, neurological impairment, hepatosplenomegaly, proximal muscle weakness, joint rigidity, cardiopathy, dysostosis multiplex, macular degeneration, retinopathy, and hearing loss. The biochemical diagnosis was confirmed at 5.11 years by fluorimetry in dried blood spot. Next generation sequencing of the IDS by Illumina platform and MLPA analyses of the IDS gene did not reveal any clinically significant variant. Sanger sequencing followed by gel electrophoresis revealed a complex rearrangement within intron 3 and intron 7 of the IDS gene and the IDS2 pseudogene. This rearrangement have already been described in the literature. The patient died with 6.1 years of age due to pneumonia. In conclusion, we should be carefull when using solely next generation sequencing approaches for the molecular diagnosis of MPS II patients or MLPA taking into consideration the limitations of these methodologies for the identification of complex rearrangements. The delay in diagnosis of this patient contributed to his premature death due to the lack of treatment that could have helped to delay disease progression if started early. |
| Databáze: | OpenAIRE |
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