2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Diagnostic challenges in diverse populations: When genetic testing doesn't tell the full story

Pdf Summary

This case study highlights the diagnostic challenges faced in diverse populations when using genetic testing. The patient, a 16-year-old Hmong male, presented with weakness in his hands and feet. His medical history included sensorineural hearing loss, short stature, and growth hormone deficiency. Diagnostic evaluations, including chromosomal microarray and whole exome sequencing, revealed two likely pathogenic variants in the GALNS and MRPS23 genes. These variants are associated with Morquio syndrome type A and combined oxidative phosphorylation deficiency type 46, respectively.<br /><br />However, the patient's phenotype did not completely match the classic presentations of these syndromes, raising questions about the accuracy of the genetic diagnosis. The study emphasizes that in diverse populations, diagnostic challenges are exacerbated due to decreased representation in variant databases and limited phenotypic data. The Hmong population, for example, has limited genomic representation.<br /><br />The case also highlights the need for further research and improvement in variant databases, as well as the inclusion of diverse populations in research studies. The study concludes that the patient is likely to have a mitochondrial disorder, but the clinical course remains unclear due to limited published data on pathogenic variants in MRPS23.<br /><br />In summary, this case study emphasizes the challenges faced in diagnosing genetic disorders in diverse populations. Phenotypic presentations may be altered by ethnic backgrounds, and variant databases may not fully capture variants that occur in diverse populations. More research, phenotypic studies, and improvements in variant databases are needed to better understand and diagnose genetic disorders in diverse populations.

Asset Subtitle

Presenting Author - Kelly L. Jones, MD; Co-Author - Erin Syverson, MGC, CGC; Co-Author - Dominic Fee, MD;

Meta Tag

Biochemical genetics

Dysmorphology

Exome sequencing

Genetic Testing

Genotype-Phenotype Correlations

Lysosomal Diseases

Metabolic Disorder

Phenotype

Sequencing

Co-Author Erin Syverson, MGC, CGC

Co-Author Dominic Fee, MD

Presenting Author Kelly L. Jones, MD

Keywords

genetic testing

diagnostic challenges

diverse populations

Hmong population

phenotypic presentations

variant databases

Morquio syndrome type A

combined oxidative phosphorylation deficiency type 46

mitochondrial disorder

pathogenic variants