DMD-related muscular dystrophy in Cameroon: Clinical and genetic profiles.
Africa
Cameroon
Duchenne muscular dystrophy
clinical patterns
genetics
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
10
04
2020
revised:
20
05
2020
accepted:
26
05
2020
pubmed:
17
6
2020
medline:
11
5
2021
entrez:
17
6
2020
Statut:
ppublish
Résumé
Most of the previous studies on Duchenne Muscular Dystrophy (DMD) were conducted in Caucasian, Asian, and Arab populations. Therefore, little is known about the features of this disease in Africans. In this study, we aimed to determine the clinical characteristics of DMD, and the common mutations associated with this condition in a group of Cameroonian patients. We recruited DMD patients and performed a general physical examination on each of them. Multiplex ligand-dependant probe amplification was carried out to investigate exon deletions and duplications in the DMD gene (OMIM: 300377) of patients and their mothers. A total of 17 male patients from 14 families were recruited, aged 14 ± 5.1 (8-23) years. The mean age at onset of symptoms was 4.6 ± 1.5 years, and the mean age at diagnosis was 12.1 ± 5.2 years. Proximal muscle weakness was noted in all patients and calf hypertrophy in the large majority of them (88.2%; 15/17). Flexion contractures were particularly frequent on the ankle (85.7%; 12/14). Wasting of shoulder girdle and thigh muscles was present in 50% (6/12) and 46.2% (6/13) of patients, respectively. No patient presented with hearing impairment. Deletions in DMD gene (OMIM: 300377) occurred in 45.5% of patients (5/11), while duplications were observed in 27.3% (3/11). Both mutation types were clustered between exons 45 and 50, and the proportion of de novo mutation was estimated at 18.2% (2/11). Despite the first symptoms of DMD occurring in infancy, the diagnosis is frequently made later in adolescence, indicating an underestimation of the number of cases of DMD in Cameroon. Future screening of deletions and duplications in patients from Cameroon should focus on the distal part of the gene.
Sections du résumé
BACKGROUND
Most of the previous studies on Duchenne Muscular Dystrophy (DMD) were conducted in Caucasian, Asian, and Arab populations. Therefore, little is known about the features of this disease in Africans. In this study, we aimed to determine the clinical characteristics of DMD, and the common mutations associated with this condition in a group of Cameroonian patients.
METHODS
We recruited DMD patients and performed a general physical examination on each of them. Multiplex ligand-dependant probe amplification was carried out to investigate exon deletions and duplications in the DMD gene (OMIM: 300377) of patients and their mothers.
RESULTS
A total of 17 male patients from 14 families were recruited, aged 14 ± 5.1 (8-23) years. The mean age at onset of symptoms was 4.6 ± 1.5 years, and the mean age at diagnosis was 12.1 ± 5.2 years. Proximal muscle weakness was noted in all patients and calf hypertrophy in the large majority of them (88.2%; 15/17). Flexion contractures were particularly frequent on the ankle (85.7%; 12/14). Wasting of shoulder girdle and thigh muscles was present in 50% (6/12) and 46.2% (6/13) of patients, respectively. No patient presented with hearing impairment. Deletions in DMD gene (OMIM: 300377) occurred in 45.5% of patients (5/11), while duplications were observed in 27.3% (3/11). Both mutation types were clustered between exons 45 and 50, and the proportion of de novo mutation was estimated at 18.2% (2/11).
CONCLUSION
Despite the first symptoms of DMD occurring in infancy, the diagnosis is frequently made later in adolescence, indicating an underestimation of the number of cases of DMD in Cameroon. Future screening of deletions and duplications in patients from Cameroon should focus on the distal part of the gene.
Identifiants
pubmed: 32543101
doi: 10.1002/mgg3.1362
pmc: PMC7434738
doi:
Substances chimiques
DMD protein, human
0
Dystrophin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1362Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG009716
Pays : United States
Organisme : NHLBI NIH HHS
ID : U24 HL135600
Pays : United States
Organisme : Wellcome Trust
ID : H3A/18/001
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
Références
Orphanet J Rare Dis. 2017 Aug 31;12(1):149
pubmed: 28859693
J Am Coll Cardiol. 2013 Mar 5;61(9):948-54
pubmed: 23352781
Neuromuscul Disord. 1991;1(1):19-29
pubmed: 1822774
J Trop Pediatr. 2014 Apr;60(2):112-7
pubmed: 24213305
J Korean Med Sci. 2012 Mar;27(3):274-80
pubmed: 22379338
Curr Genomics. 2018 Aug;19(5):327-338
pubmed: 30065609
PLoS One. 2014 May 15;9(5):e93919
pubmed: 24832127
Am J Hum Genet. 1994 Oct;55(4):685-94
pubmed: 7942846
Hepat Mon. 2012 Nov;12(11):e7711
pubmed: 23346152
Neurologia. 2017 Jul - Aug;32(6):377-385
pubmed: 26968818
J Med Genet. 1980 Jun;17(3):165-9
pubmed: 7401126
Neurodegener Dis Manag. 2019 Jun;9(3):123-133
pubmed: 31166138
J Paediatr Child Health. 2015 Aug;51(8):759-64
pubmed: 25752877
Hum Mutat. 2006 Sep;27(9):938-45
pubmed: 16917894
Dev Med Child Neurol. 1973 Aug;15(4):500-5
pubmed: 4732900
S Afr Med J. 1994 Aug;84(8 Pt 1):494-7
pubmed: 7825085
J Genet. 2004 Dec;83(3):235-44
pubmed: 15689625
J Med Genet. 1978 Oct;15(5):339-45
pubmed: 739522
J Neurol Sci. 1992 Jan;107(1):60-4
pubmed: 1578235
Nucleic Acids Res. 1988 Feb 11;16(3):1215
pubmed: 3344216
Indian J Med Res. 2010 Sep;132:303-11
pubmed: 20847377
Neuromuscul Disord. 2014 Jun;24(6):482-91
pubmed: 24780148
Indian J Pediatr. 2018 Apr;85(4):276-281
pubmed: 28653137
Clin Biochem. 1999 Feb;32(1):77-80
pubmed: 10074896
J Neurol Sci. 1985 Dec;71(2-3):225-31
pubmed: 4087024
Neurology. 1991 Dec;41(12):1878-81
pubmed: 1745341
Muscle Nerve. 2006 Aug;34(2):135-44
pubmed: 16770791
PLoS One. 2012;7(11):e48864
pubmed: 23155419
PLoS One. 2009;4(2):e4347
pubmed: 19194511
J Neurocytol. 1995 Aug;24(8):625-32
pubmed: 7595670
J Clin Lab Anal. 2018 Sep;32(7):e22445
pubmed: 29604111
Laryngoscope. 1997 Aug;107(8):1053-6
pubmed: 9261007
Gac Med Mex. 1994 Nov-Dec;130(6):459-64
pubmed: 7557061
BMC Med Genet. 2019 Aug 14;20(1):139
pubmed: 31412794
J Clin Neurol. 2017 Jan;13(1):91-97
pubmed: 28079318
Arch Dis Child. 1965 Jun;40(211):296-301
pubmed: 21032424
Hum Hered. 1998 Mar-Apr;48(2):61-6
pubmed: 9526164
J Med Genet. 2016 Mar;53(3):145-51
pubmed: 26754139
Neuromuscul Disord. 1994 Jul;4(4):359-69
pubmed: 7981593
J Neurol Sci. 1967 May-Jun;4(3):435-44
pubmed: 6051754
Am J Med Genet. 1995 Nov 6;59(2):182-7
pubmed: 8588583
J Pediatr. 2009 Sep;155(3):380-5
pubmed: 19394035
Cardiology. 2003;99(1):1-19
pubmed: 12589117
Yonsei Med J. 2006 Apr 30;47(2):184-90
pubmed: 16642546
Am J Med Genet. 1994 Feb 15;49(4):369-73
pubmed: 8160727
Genome Res. 2012 Jan;22(1):25-34
pubmed: 22090376
Laryngoscope. 1999 May;109(5):730-5
pubmed: 10334222
Neurol India. 2019 May-Jun;67(3):714-715
pubmed: 31347541
Muscle Nerve. 1983 Feb;6(2):91-103
pubmed: 6343858
Cent Afr J Med. 1981 Sep;27(9):174-6
pubmed: 7307074
Neuromuscul Disord. 2017 Feb;27(2):107-114
pubmed: 28003112
Eur J Med Genet. 2011 Jul-Aug;54(4):e399-404
pubmed: 21473937
Mol Vis. 2012;18:2022-32
pubmed: 22876130
Ann Indian Acad Neurol. 2014 Jul;17(3):303-7
pubmed: 25221400
J Cell Biol. 2013 May 13;201(4):499-510
pubmed: 23671309
J Pediatr Neurol. 2018 Aug;16(4):222-231
pubmed: 30923442
Am J Med Genet. 1980;7(1):27-34
pubmed: 7211951
Indian Pediatr. 2015 Jun;52(6):481-4
pubmed: 26121722
Z Orthop Ihre Grenzgeb. 2000 Mar-Apr;138(2):131-5
pubmed: 10820878
J Med Genet. 1983 Feb;20(1):1-11
pubmed: 6842530
Neuromuscul Disord. 2017 May;27(5):447-451
pubmed: 28262469
Am J Hum Genet. 1990 Apr;46(4):682-95
pubmed: 2316519
BMC Med Genet. 2019 Nov 14;20(1):180
pubmed: 31727011
Can Med Assoc J. 1976 Oct 23;115(8):749-52
pubmed: 974964
Pediatr Rev. 2006 Mar;27(3):83-8
pubmed: 16510548
Clin Genet. 1999 May;55(5):376-80
pubmed: 10422811
J Neurol Sci. 1991 Apr;102(2):190-6
pubmed: 2072118
Brain. 2011 Dec;134(Pt 12):3547-59
pubmed: 22102647
Neuromuscul Disord. 1996 Oct;6(5):367-76
pubmed: 8938701
Orphanet J Rare Dis. 2018 Jul 4;13(1):109
pubmed: 29973226
Neurol India. 2009 Nov-Dec;57(6):734-8
pubmed: 20139501
Mol Genet Genomic Med. 2020 Aug;8(8):e1362
pubmed: 32543101
Indian J Med Res. 2013 Jun;137(6):1102-10
pubmed: 23852291
PLoS One. 2018 May 30;13(5):e0197205
pubmed: 29847600
J Community Genet. 2011 Mar;2(1):33-42
pubmed: 22109722
Neuromuscul Disord. 2019 Apr;29(4):317-320
pubmed: 30926200