Phenotypic presentation of Mendelian disease across the diagnostic trajectory in electronic health records

Tinker, Richard; Peterson, Josh F.; Bastarache, Lisa

doi:10.1016/j.gim.2023.100921

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…This curation process is part of a larger VUMC project called the clinical genetic database (CGDB). This comprehensive database has been used for previous studies Tinker, Peterson, & Bastarache, 2023). All findings for genetic tests for XL genes were reviewed to establish their clinical interpretation.…”

Section: Creating a Database Of Genetic Diseases Using A Vumc Ehr Cohortmentioning

confidence: 99%

Data from electronic healthcare records expand our understanding of X‐linked genetic diseases

Tinker,

Bastarache,

Ezell

et al. 2024

American J of Med Genetics Pt A

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Disease specific cohort studies have reported details on X linked (XL) disorders affecting females. We investigated the spectrum and penetrance of XL disorders seen in electronic health records (EHR). We generated a cohort of individuals diagnosed with XL disorders at Vanderbilt University Medical Center over 20 years. Our cohort included 477 males and 203 females diagnosed with 108 different XL genetic disorders. We found large differences between the female/male (F/M) ratios for various XL disorders regardless of their OMIM annotated mode of inheritance. We identified four XL recessive disorders affecting women previously only described in men. Biomarkers for XL disease had unique gender‐specific patterns differing between modes of inheritance. EHRs provide large cohorts of XL genetic disorders that give new insights compared to the literature. Differences in the F/M ratios and biomarkers of XL disorders observed likely result from disease specific and sex dependent penetrance. We conclude that observed gender ratios associated with specific XL disorders may be more useful than those predicted by Mendelian genetics provided by OMIM. Our findings of a gender specific penetrance and severity for XL disorders show unexpected differences from Mendelian predictions. Further work is required to validate our findings in larger combined EHR cohorts.

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Section: Creating a Database Of Genetic Diseases Using A Vumc Ehr Cohortmentioning

confidence: 99%