Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Nov;21(11):2512-2520.
doi: 10.1038/s41436-019-0544-8. Epub 2019 May 20.

Estimating prevalence for limb-girdle muscular dystrophy based on public sequencing databases

Wei Liu  1 , Sander Pajusalu #  2   3   4 , Nicole J Lake #  2   5 , Geyu Zhou  1 , Nilah Ioannidis  6   7 , Plavi Mittal  6   8 , Nicholas E Johnson  9 , Conrad C Weihl  10 , Bradley A Williams  6 , Douglas E Albrecht  6 , Laura E Rufibach  6 , Monkol Lek  11
Affiliations
Free article

Estimating prevalence for limb-girdle muscular dystrophy based on public sequencing databases

Wei Liu et al. Genet Med. 2019 Nov.
Free article

Abstract

Purpose: Limb-girdle muscular dystrophies (LGMD) are a genetically heterogeneous category of autosomal inherited muscle diseases. Many genes causing LGMD have been identified, and clinical trials are beginning for treatment of some genetic subtypes. However, even with the gene-level mechanisms known, it is still difficult to get a robust and generalizable prevalence estimation for each subtype due to the limited amount of epidemiology data and the low incidence of LGMDs.

Methods: Taking advantage of recently published exome and genome sequencing data from the general population, we used a Bayesian method to develop a robust disease prevalence estimator.

Results: This method was applied to nine recessive LGMD subtypes. The estimated disease prevalence calculated by this method was largely comparable with published estimates from epidemiological studies; however, it highlighted instances of possible underdiagnosis for LGMD2B and 2L.

Conclusion: The increasing size of aggregated population variant databases will allow for robust and reproducible prevalence estimates of recessive disease, which is critical for the strategic design and prioritization of clinical trials.

Keywords: disease prevalence; limb-girdle muscular dystrophy; rare disease.

PubMed Disclaimer

References

    1. Vissing J. Limb girdle muscular dystrophies: classification, clinical spectrum and emerging therapies. Curr Opin Neurol. 2016;29:635–641.
    1. Nallamilli BRR, Chakravorty S, Kesari A, et al. Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients. Ann Clin Transl Neurol. 2018;5:1574–1587.
    1. Stence A, Westra S, Mathews KD, et al. Limb-girdle muscular dystrophy in the United States. J Neuropathol Exp Neurol. 2006;65:995–1003.
    1. Magri F, Nigro V, Angelini C, et al. The Italian Limb Girdle Muscular Dystrophy Registry: relative frequency, clinical features, and differential diagnosis. Muscle Nerve. 2017;55:55–68.
    1. Emery AE. Population frequencies of inherited neuromuscular diseases—a world survey. Neuromuscul Disord. 1991;1:19–29.

Publication types

LinkOut - more resources