Publications by authors named "Annabelle Arlt"
Pathogenic, biallelic variants in were identified in 2020 as a novel cause for autosomal-recessive Charcot-Marie-Tooth disease (CMT) type 2, an inherited neuropathy. codes for the enzyme sorbitol dehydrogenase. Loss of this enzyme's activity leads to an increase of sorbitol in serum.
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- Dysmorphologists face challenges due to the diverse phenotypic variability of human faces, particularly when using Next-Generation Phenotyping (NGP) tools, which are often trained on limited data.
- To address this, the GestaltMatcher Database (GMDB) was created, compiling over 10,980 facial images from various global populations, significantly improving the representation of underrepresented ancestries, especially African and Asian patients.
- The study found that incorporating data from non-European patients enhanced NGP accuracy by over 11% without compromising performance for European patients, highlighting the importance of diverse datasets in identifying genetic disorders.
Next-generation phenotyping (NGP) can be used to compute the similarity of dysmorphic patients to known syndromic diseases. So far, the technology has been evaluated in variant prioritization and classification, providing evidence for pathogenicity if the phenotype matched with other patients with a confirmed molecular diagnosis. In a Nigerian cohort of individuals with facial dysmorphism, we used the NGP tool GestaltMatcher to screen portraits prior to genetic testing and subjected individuals with high similarity scores to exome sequencing (ES).
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- The significant phenotypic variability of human faces complicates the work of dysmorphologists by challenging Next-Generation Phenotyping (NGP) tools, especially when analyzing patients from diverse genetic backgrounds.
- The research established the GestaltMatcher Database (GMDB), which includes over 10,000 facial images from patients with rare genetic disorders worldwide, striving to improve representation of underrepresented populations, particularly Asian and African patients.
- The analysis showed that incorporating data from non-European patients enhanced the accuracy of NGP in diagnosing facial disorders without negatively affecting performance on European patients, emphasizing the need for more diverse datasets in medical genetics.
Article Synopsis
- - Goltz syndrome (GS) is a rare X-linked disorder caused by mutations in the PORCN gene, leading to a range of symptoms including skin and skeletal abnormalities, developmental delays, and neurological issues, especially in males who often experience in utero lethality.
- - Two case studies are presented: one girl with typical GS features and severe developmental issues from a PORCN mutation, and a boy exhibiting fewer skin symptoms but significant neurological problems linked to a novel PORCN mutation.
- - The findings point to the need for more genetic and functional analysis of GS cases, indicating that some mutations may have incomplete penetrance, and highlight the importance of CNS vulnerabilities in diagnosis.
Article Synopsis
- Recent research has identified congenital myasthenic syndromes (CMS) due to genetic variants that hinder acetylcholine (ACh) synthesis and recycling, specifically involving the vesicular ACh transporter (VAChT).
- A study on a 5-year-old patient through exome sequencing revealed two harmful genetic variants, correlating with severe motor and cognitive deficits, and muscle biopsy showed abnormal fiber size and lipid accumulation.
- The findings suggest that nonsense variants have a more negative impact on CMS symptoms, affecting muscle integrity and highlighting the critical role of VAChT in maintaining ACh levels and lipid balance in muscle cells.