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. 2020 Jan 13;15(1):11.
doi: 10.1186/s13023-019-1291-2.

The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease

Jorge A Bevilacqua  1   2   3 , Maria Del Rosario Guecaimburu Ehuletche  4 , Abayuba Perna  5 , Alberto Dubrovsky  6 , Marcondes C Franca Jr  7 , Steven Vargas  8 , Madhuri Hegde  9 , Kristl G Claeys  10   11 , Volker Straub  12 , Nadia Daba  13 , Roberta Faria  14 , Magali Periquet  15 , Susan Sparks  16 , Nathan Thibault  16 , Roberto Araujo  17
Affiliations

The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease

Jorge A Bevilacqua et al. Orphanet J Rare Dis. .

Abstract

Background: Limb-girdle muscular dystrophy (LGMD) is a group of neuromuscular disorders of heterogeneous genetic etiology with more than 30 directly related genes. LGMD is characterized by progressive muscle weakness involving the shoulder and pelvic girdles. An important differential diagnosis among patients presenting with proximal muscle weakness (PMW) is late-onset Pompe disease (LOPD), a rare neuromuscular glycogen storage disorder, which often presents with early respiratory insufficiency in addition to PMW. Patients with PMW, with or without respiratory symptoms, were included in this study of Latin American patients to evaluate the profile of variants for the included genes related to LGMD recessive (R) and LOPD and the frequency of variants in each gene among this patient population.

Results: Over 20 institutions across Latin America (Brazil, Argentina, Peru, Ecuador, Mexico, and Chile) enrolled 2103 individuals during 2016 and 2017. Nine autosomal recessive LGMDs and Pompe disease were investigated in a 10-gene panel (ANO5, CAPN3, DYSF, FKRP, GAA, SGCA, SGCB, SGCD, SGCG, TCAP) based on reported disease frequency in Latin America. Sequencing was performed with Illumina's NextSeq500 and variants were classified according to ACMG guidelines; pathogenic and likely pathogenic were treated as one category (P) and variants of unknown significance (VUS) are described. Genetic variants were identified in 55.8% of patients, with 16% receiving a definitive molecular diagnosis; 39.8% had VUS. Nine patients were identified with Pompe disease.

Conclusions: The results demonstrate the effectiveness of this targeted genetic panel and the importance of including Pompe disease in the differential diagnosis for patients presenting with PMW.

Keywords: Latin America; Limb-girdle muscle weakness; Next-generation sequencing; Pompe disease.

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Conflict of interest statement

JAB has received lecture fees from Sanofi-Genzyme; MRGE has nothing to disclose; AP has received funding from Sanofi Genzyme; AD has taken part in advisory boards and given lectures for Sanofi Genzyme; MF has taken part in advisory boards and given lectures for Sanofi Genzyme; SV has received grant/research support, has served as a consultant, and served on the speakers bureau for Sanofi Genzyme; MH has nothing to disclose; KGC received travel and research grant from Sanofi Genzyme, unrelated to this study; VS has received speaker honoraria from Sanofi Genzyme and funding for a collaborative sequencing project unrelated to this study; ND, RF, MP, SS, NT, and RA are employees of Sanofi Genzyme and Sanofi shareholders.

Figures

Fig. 1
Fig. 1
Percentages for each genetic variant and each intronic variant within the total population. 1173 (55.8%) patients had genetic variants identified by the panel
Fig. 2
Fig. 2
Frequencies and percentages of patients with confirmed molecular diagnosis, negative diagnosis, or variants of unknown significance (VUS)
See this image and copyright information in PMC

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