TY - JOUR
T1 - Mutation pattern in 606 Duchenne muscular dystrophy children with a comparison between familial and non-familial forms
T2 - a study in an Indian large single-center cohort
AU - Polavarapu, Kiran
AU - Preethish-Kumar, Veeramani
AU - Sekar, Deepha
AU - Vengalil, Seena
AU - Nashi, Saraswati
AU - Mahajan, Niranjan P.
AU - Thomas, Priya Treesa
AU - Sadasivan, Arun
AU - Warrier, Manjusha
AU - Gupta, Anupam
AU - Arunachal, Gautham
AU - Debnath, Monojit
AU - Keerthipriya, Muddasu Suhasini
AU - Pradeep-Chandra-Reddy, Chevula
AU - Puttegowda, Arpitha
AU - John, Anu P.
AU - Tavvala, Ajitha
AU - Gunasekaran, Swetha
AU - Sathyaprabha, Talakad N.
AU - Chandra, Sadanandavalli Retnaswami
AU - Kramer, Boris
AU - Delhaas, Tammo
AU - Nalini, Atchayaram
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/9
Y1 - 2019/9
N2 - Introduction Duchenne muscular dystrophy (DMD) is induced by a wide spectrum of mutations such as exon deletions, duplications and small mutations in the dystrophin gene. This is the first study on the mutational spectrum in a cohort of DMD children from India, with an emphasis to compare the mutations in familial and sporadic forms. Results Multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS) identified 525 and 70 cases of DMD, respectively, while 11 cases showed absent dystrophin staining with no mutations detected. Families with two or more affected males contributed to 12% of the entire cohort. The mutations comprised of exonic deletions in 492/606 (81.2%), duplications in 33/606 (5.4%) and small mutations (point mutations and INDELs) in 70/606 (11.5%) cases. MLPA identified significantly more larger mutations in sporadic (88.2%) than in familial cases (75.3%). The mutations in NGS were: [nonsense = 40 (57.1%); frameshift = 17 (24.3%); splice variant = 12 (17.1%)]. Nonsense mutations were more common in familial than in sporadic cases: 17.8% vs 10.7%. The familial group reported an earlier onset of disease (2.8 +/- 1.7 years) as compared to sporadic cases (3.8 +/- 1.6 years). Conclusion MLPA could identify mutations in a high percentage of our DMD children. The preponderance of small mutations was noted to be distinctly higher in the familial group. Intriguingly, the familial form of DMD formed a small percentage of the entire cohort. The reasons could be increasing awareness among parents and physicians with early identification of DMD cases, genetic counseling and prenatal testing.
AB - Introduction Duchenne muscular dystrophy (DMD) is induced by a wide spectrum of mutations such as exon deletions, duplications and small mutations in the dystrophin gene. This is the first study on the mutational spectrum in a cohort of DMD children from India, with an emphasis to compare the mutations in familial and sporadic forms. Results Multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS) identified 525 and 70 cases of DMD, respectively, while 11 cases showed absent dystrophin staining with no mutations detected. Families with two or more affected males contributed to 12% of the entire cohort. The mutations comprised of exonic deletions in 492/606 (81.2%), duplications in 33/606 (5.4%) and small mutations (point mutations and INDELs) in 70/606 (11.5%) cases. MLPA identified significantly more larger mutations in sporadic (88.2%) than in familial cases (75.3%). The mutations in NGS were: [nonsense = 40 (57.1%); frameshift = 17 (24.3%); splice variant = 12 (17.1%)]. Nonsense mutations were more common in familial than in sporadic cases: 17.8% vs 10.7%. The familial group reported an earlier onset of disease (2.8 +/- 1.7 years) as compared to sporadic cases (3.8 +/- 1.6 years). Conclusion MLPA could identify mutations in a high percentage of our DMD children. The preponderance of small mutations was noted to be distinctly higher in the familial group. Intriguingly, the familial form of DMD formed a small percentage of the entire cohort. The reasons could be increasing awareness among parents and physicians with early identification of DMD cases, genetic counseling and prenatal testing.
KW - Duchenne muscular dystrophy
KW - Familial
KW - Mutation
KW - India
KW - DMD GENE
KW - DATABASE
KW - DIAGNOSIS
U2 - 10.1007/s00415-019-09380-3
DO - 10.1007/s00415-019-09380-3
M3 - Article
C2 - 31139960
SN - 0340-5354
VL - 266
SP - 2177
EP - 2185
JO - Journal of Neurology
JF - Journal of Neurology
IS - 9
ER -