Publications by authors named "Laura Dempsey-Nunez"

Using whole-exome sequencing, we identified homozygous mutations in two unlinked genes, SEC23A c.1200G>C (p.M400I) and MAN1B1 c.

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Background: Late-onset Pompe disease (LOPD) is a rare treatable lysosomal storage disorder characterized by progressive lysosomal glycogen accumulation and muscle weakness, with often a limb-girdle pattern. Despite published guidelines, testing for LOPD is often overlooked or delayed in adults, owing to its low frequency compared to other muscle disorders with similar muscle patterns. Next-generation sequencing has the capability to test concurrently for several muscle disorders.

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  • Isolated methylmalonic aciduria (MMA) is caused by defects in the enzyme methylmalonylCoA mutase or issues with converting vitamin B12 into its active form, adenosylcobalamin, often linked to mutations in the MMAB gene.
  • Diagnosing MMA typically involves testing the function of methylmalonylCoA mutase in patient cells, but some patients, like the one described, showed undiagnosed cases that led to the identification of mutations through gene sequencing.
  • A new high resolution melting analysis was developed to detect MMAB mutations in patient samples, confirming mutations in known cblB patients and identifying mutations in some previously undiagnosed patients, suggesting traditional testing might miss some mild
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Three deceased infants from a Pakistani consanguineous family presented with a similar phenotype of cholestatic liver disease, hypotonia, severe failure to thrive, recurrent vomiting, renal tubulopathy, and a progressive neurodegenerative course. Mitochondrial DNA depletion syndrome was considered in view of multisystem involvement. Exome sequencing, revealed a homozygous novel mutation c.

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  • The MMAA gene is essential for the metabolism of cobalamin (vitamin B12), and mutations in this gene cause a type of disorder known as cblA, which is associated with excessive methylmalonic acid in the urine.
  • A high-resolution melting analysis (HRMA) was developed to quickly identify mutations in the MMAA gene among various patient groups and confirmed variants through Sanger sequencing.
  • The study identified new variants, including ten previously unreported mutations, all of which are predicted to be damaging, highlighting the potential limitations of current diagnostic methods for mild cases of cblA disorders.
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  • An infant with severe health issues, including megaloblastic anemia and immune deficiency, was studied to understand the underlying genetic cause.
  • Exome sequencing revealed two mutations in the MTHFD1 gene, critical for folate metabolism, one affecting a splice site and the other changing a vital amino acid.
  • The findings indicate a unique genetic disorder impacting folate metabolism, highlighting the importance of advanced genetic analysis techniques like exome sequencing for identifying rare genetic conditions.
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Background: Combined Malonic and Methylmalonic Aciduria (CMAMMA) is a rare recessive inborn error of metabolism characterised by elevations of urine malonic acid (MA) and methylmalonic acid (MMA). Nearly all reported cases are caused by malonyl-CoA decarboxylase (MCD) deficiency. Most patients have metabolic acidosis, developmental delay, seizures and cardiomyopathy.

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