Skip to main content
Top

08-06-2024 | Original Article

Investigation of genotype-phenotype and familial features of Turkish dystrophinopathy patients

Authors: Hande Ozkalayci, Elcin Bora, Tufan Cankaya, Mehmet Kocabey, Nadide Cemre Zubari, Uluc Yis, Ozlem Giray Bozkaya, Serkan Turan, Aynur Pekcanlar Akay, Ahmet Okay Caglayan, Ayfer Ulgenalp

Published in: Neurogenetics

Login to get access

Abstract

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive allelic muscle diseases caused by dystrophin gene mutations. Eight hundred thirty-seven patients admitted between 1997 and 2022 were included in the study. Two hundred twenty patients were analyzed by multiplex PCR (mPCR) alone. Five hundred ninety-five patients were investigated by multiplex ligation-dependent probe amplification (MLPA), and 54 patients were examined by sequencing. Deletion was detected in 60% (132/220) of the cases in the mPCR group only and in 58.3% (347/595) of the cases with MLPA analysis. The rates of deletion and duplication were 87.7% and 12.3%, respectively, in the MLPA analysis. Single exon deletions were the most common mutation type. The introns 43–55 (81.8%) and exons 2–21 (13.1%) regions were detected as hot spots in deletions. It was determined that 89% of the mutations were suitable for exon skipping therapy. The reading frame rule did not hold in 7.6% of D/BMD cases (17/224). We detected twenty-five pathogenic/likely pathogenic variants in sequencing, five of which were novel variants. Nonsense mutation was the most common small mutation (44%). 21% of DMD patients were familial. We detected germline mosaicism in four families (4.3%) in the large rearrangement group and one gonosomal mosaicism in a family with a nonsense mutation. This is the largest study examining genotype and phenotype data in Turkish D/BMD families investigated by MLPA analysis. The reading frame hypothesis is not valid in all cases. Sharing the genotype and phenotype characteristics of these cases in the literature will shed light on the molecular structure of DMD and guide gene therapy research. In genetic counseling, carrier screening in the family and possible gonadal mosaicism should be emphasized.
Appendix
Available only for authorised users
Literature
2.
go back to reference Mendell JR, Shilling C, Leslie ND, Flanigan KM, al-Dahhak R, Gastier-Foster J et al (2012) Evidence-based path to newborn screening for Duchenne muscular dystrophy. Ann Neurol 71(3):304–313PubMedCrossRef Mendell JR, Shilling C, Leslie ND, Flanigan KM, al-Dahhak R, Gastier-Foster J et al (2012) Evidence-based path to newborn screening for Duchenne muscular dystrophy. Ann Neurol 71(3):304–313PubMedCrossRef
3.
go back to reference Bushby KM, Thambyayah M, Gardner-Medwin D (1991) Prevalence and incidence of Becker muscular dystrophy. Lancet 337(8748):1022–1024PubMedCrossRef Bushby KM, Thambyayah M, Gardner-Medwin D (1991) Prevalence and incidence of Becker muscular dystrophy. Lancet 337(8748):1022–1024PubMedCrossRef
5.
6.
go back to reference Hoogerwaard EM, Bakker E, Ippel PF, Oosterwijk JC, Majoor-Krakauer DF, Leschot NJ et al (1999) Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the Netherlands: a cohort study. Lancet 353(9170):2116–2119PubMedCrossRef Hoogerwaard EM, Bakker E, Ippel PF, Oosterwijk JC, Majoor-Krakauer DF, Leschot NJ et al (1999) Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the Netherlands: a cohort study. Lancet 353(9170):2116–2119PubMedCrossRef
7.
go back to reference Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM (1987) Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50(3):509–517PubMedCrossRef Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM (1987) Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50(3):509–517PubMedCrossRef
8.
go back to reference Roberts RG, Coffey AJ, Bobrow M, Bentley DR (1993) Exon structure of the human dystrophin gene. Genomics 16(2):536–538PubMedCrossRef Roberts RG, Coffey AJ, Bobrow M, Bentley DR (1993) Exon structure of the human dystrophin gene. Genomics 16(2):536–538PubMedCrossRef
9.
go back to reference Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53(2):219–228PubMedCrossRef Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53(2):219–228PubMedCrossRef
10.
go back to reference Monaco AP, Bertelson CJ, Liechti-Gallati S, Moser H, Kunkel LM (1988) An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 2(1):90–95PubMedCrossRef Monaco AP, Bertelson CJ, Liechti-Gallati S, Moser H, Kunkel LM (1988) An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 2(1):90–95PubMedCrossRef
11.
go back to reference Koenig M, Beggs AH, Moyer M, Scherpf S, Heindrich K, Bettecken T et al (1989) The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet 45(4):498–506PubMedPubMedCentral Koenig M, Beggs AH, Moyer M, Scherpf S, Heindrich K, Bettecken T et al (1989) The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet 45(4):498–506PubMedPubMedCentral
12.
go back to reference Tuffery-Giraud S, Beroud C, Leturcq F, Yaou RB, Hamroun D, Michel-Calemard L et al (2009) Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase. Hum Mutat 30(6):934–945PubMedCrossRef Tuffery-Giraud S, Beroud C, Leturcq F, Yaou RB, Hamroun D, Michel-Calemard L et al (2009) Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase. Hum Mutat 30(6):934–945PubMedCrossRef
13.
go back to reference Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K, Kosma K et al (2015) The TREAT-NMD DMD Global Database: analysis of more than 7,000 duchenne muscular dystrophy mutations. Hum Mutat 36(4):395–402PubMedPubMedCentralCrossRef Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K, Kosma K et al (2015) The TREAT-NMD DMD Global Database: analysis of more than 7,000 duchenne muscular dystrophy mutations. Hum Mutat 36(4):395–402PubMedPubMedCentralCrossRef
14.
go back to reference Chamberlain JS, Gibbs RA, Ranier JE, Nguyen PN, Caskey CT (1988) Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res 16(23):11141–11156PubMedPubMedCentralCrossRef Chamberlain JS, Gibbs RA, Ranier JE, Nguyen PN, Caskey CT (1988) Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res 16(23):11141–11156PubMedPubMedCentralCrossRef
15.
go back to reference Beggs AH, Koenig M, Boyce FM, Kunkel LM (1990) Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Hum Genet 86:45–48PubMedCrossRef Beggs AH, Koenig M, Boyce FM, Kunkel LM (1990) Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Hum Genet 86:45–48PubMedCrossRef
16.
go back to reference Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30(12):e57PubMedPubMedCentralCrossRef Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30(12):e57PubMedPubMedCentralCrossRef
17.
18.
go back to reference Toksoy G, Durmus H, Aghayev A, Bagirova G, Sevinc Rustemoglu B, Basaran S et al (2019) Mutation spectrum of 260 dystrophinopathy patients from Turkey and important highlights for genetic counseling. Neuromuscul Disord 29(8):601–613PubMedCrossRef Toksoy G, Durmus H, Aghayev A, Bagirova G, Sevinc Rustemoglu B, Basaran S et al (2019) Mutation spectrum of 260 dystrophinopathy patients from Turkey and important highlights for genetic counseling. Neuromuscul Disord 29(8):601–613PubMedCrossRef
19.
go back to reference Cavdarli B, Yayici Koken O, Ceylan AC, Semerci Gunduz CN, Topaloglu H (2021) Genetic Landscape of Dystrofin Gene Deletions and duplications from Turkey: a single Center experience. Turkish J Pediatr Dis 15:319–324 Cavdarli B, Yayici Koken O, Ceylan AC, Semerci Gunduz CN, Topaloglu H (2021) Genetic Landscape of Dystrofin Gene Deletions and duplications from Turkey: a single Center experience. Turkish J Pediatr Dis 15:319–324
20.
go back to reference Chamberlain JS, Gibbs RA, Ranier JE, Caskey CT (1990) Multiplex PCR for the diagnosis of Duchenne muscular dystrophy. In: Innis MA, Gelfand DH, Sninsky JJ, White TJ (eds) PCR protocols: a guide to methods and applications. Academic, San Diego, pp 272–281 Chamberlain JS, Gibbs RA, Ranier JE, Caskey CT (1990) Multiplex PCR for the diagnosis of Duchenne muscular dystrophy. In: Innis MA, Gelfand DH, Sninsky JJ, White TJ (eds) PCR protocols: a guide to methods and applications. Academic, San Diego, pp 272–281
21.
go back to reference Gibbs RA, Chamberlain JS, Caskey CT (1988) Principles and applications for DNA amplification. In: Erlich HA (ed) Diagnosis of New Mutation diseases using the polymerase chain reaction. Stocktan, New York, pp 171–191 Gibbs RA, Chamberlain JS, Caskey CT (1988) Principles and applications for DNA amplification. In: Erlich HA (ed) Diagnosis of New Mutation diseases using the polymerase chain reaction. Stocktan, New York, pp 171–191
22.
go back to reference Abbs S, Yau SC, Clark S, Mathew CG, Bobrow M (1991) A convenient multiplex PCR system for the detection of dystrophin gene deletions: a comparative analysis with cDNA hybridization shows mistypings by both methods. J Med Genet 28(5):304–311PubMedPubMedCentralCrossRef Abbs S, Yau SC, Clark S, Mathew CG, Bobrow M (1991) A convenient multiplex PCR system for the detection of dystrophin gene deletions: a comparative analysis with cDNA hybridization shows mistypings by both methods. J Med Genet 28(5):304–311PubMedPubMedCentralCrossRef
23.
go back to reference Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424PubMedPubMedCentralCrossRef Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424PubMedPubMedCentralCrossRef
28.
go back to reference Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P et al (1997) Schedule for affective disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36(7):980–988PubMedCrossRef Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P et al (1997) Schedule for affective disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36(7):980–988PubMedCrossRef
29.
go back to reference Poda M, Güçlü Geyik F, Çoban N, Tüysüz B, Güven G, Kömürcü Bayrak E et al (2017) Evaluation of dystrophin gene deletion patterns in a large Duchenne/Becker muscular dystrophy patient sample; 17 years experience from one Turkish Diagnostic Center. Deneysel Tıp Araştırma Enstitüsü Dergisi 7(14):50–61 Poda M, Güçlü Geyik F, Çoban N, Tüysüz B, Güven G, Kömürcü Bayrak E et al (2017) Evaluation of dystrophin gene deletion patterns in a large Duchenne/Becker muscular dystrophy patient sample; 17 years experience from one Turkish Diagnostic Center. Deneysel Tıp Araştırma Enstitüsü Dergisi 7(14):50–61
30.
go back to reference Juan-Mateu J, Gonzalez-Quereda L, Rodriguez MJ, Baena M, Verdura E, Nascimento A et al (2015) DMD mutations in 576 Dystrophinopathy families: a Step Forward in genotype-phenotype correlations. PLoS ONE 10(8):e0135189PubMedPubMedCentralCrossRef Juan-Mateu J, Gonzalez-Quereda L, Rodriguez MJ, Baena M, Verdura E, Nascimento A et al (2015) DMD mutations in 576 Dystrophinopathy families: a Step Forward in genotype-phenotype correlations. PLoS ONE 10(8):e0135189PubMedPubMedCentralCrossRef
31.
go back to reference Marey I, Ben Yaou R, Deburgrave N, Vasson A, Nectoux J, Leturcq F et al (2016) Non Random distribution of DMD deletion breakpoints and implication of double strand breaks repair and replication error repair mechanisms. J Neuromuscul Dis 3(2):227–245PubMedCrossRef Marey I, Ben Yaou R, Deburgrave N, Vasson A, Nectoux J, Leturcq F et al (2016) Non Random distribution of DMD deletion breakpoints and implication of double strand breaks repair and replication error repair mechanisms. J Neuromuscul Dis 3(2):227–245PubMedCrossRef
32.
go back to reference Wei X, Dai Y, Yu P, Qu N, Lan Z, Hong X et al (2014) Targeted next-generation sequencing as a comprehensive test for patients with and female carriers of DMD/BMD: a multi-population diagnostic study. Eur J Hum Genet 22(1):110–118PubMedCrossRef Wei X, Dai Y, Yu P, Qu N, Lan Z, Hong X et al (2014) Targeted next-generation sequencing as a comprehensive test for patients with and female carriers of DMD/BMD: a multi-population diagnostic study. Eur J Hum Genet 22(1):110–118PubMedCrossRef
33.
go back to reference Gualandi F, Trabanelli C, Rimessi P, Calzolari E, Toffolatti L, Patarnello T et al (2003) Multiple exon skipping and RNA circularisation contribute to the severe phenotypic expression of exon 5 dystrophin deletion. J Med Genet 40(8):e100PubMedPubMedCentralCrossRef Gualandi F, Trabanelli C, Rimessi P, Calzolari E, Toffolatti L, Patarnello T et al (2003) Multiple exon skipping and RNA circularisation contribute to the severe phenotypic expression of exon 5 dystrophin deletion. J Med Genet 40(8):e100PubMedPubMedCentralCrossRef
34.
go back to reference Yang J, Li SY, Li YQ, Cao JQ, Feng SW, Wang YY et al (2013) MLPA-based genotype-phenotype analysis in 1053 Chinese patients with DMD/BMD. BMC Med Genet 14:29PubMedPubMedCentralCrossRef Yang J, Li SY, Li YQ, Cao JQ, Feng SW, Wang YY et al (2013) MLPA-based genotype-phenotype analysis in 1053 Chinese patients with DMD/BMD. BMC Med Genet 14:29PubMedPubMedCentralCrossRef
35.
go back to reference Aartsma-Rus A, Van Deutekom JC, Fokkema IF, Van Ommen GJ, Den Dunnen JT (2006) Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve 34(2):135–144PubMedCrossRef Aartsma-Rus A, Van Deutekom JC, Fokkema IF, Van Ommen GJ, Den Dunnen JT (2006) Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve 34(2):135–144PubMedCrossRef
36.
go back to reference Fanin M, Freda MP, Vitiello L, Danieli GA, Pegoraro E, Angelini C (1996) Duchenne phenotype with in-frame deletion removing major portion of dystrophin rod: threshold effect for deletion size? Muscle Nerve 19(9):1154–1160PubMedCrossRef Fanin M, Freda MP, Vitiello L, Danieli GA, Pegoraro E, Angelini C (1996) Duchenne phenotype with in-frame deletion removing major portion of dystrophin rod: threshold effect for deletion size? Muscle Nerve 19(9):1154–1160PubMedCrossRef
37.
go back to reference Pane M, Mazzone ES, Sormani MP, Messina S, Vita GL, Fanelli L et al (2014) 6 Minute walk test in Duchenne MD patients with different mutations: 12 month changes. PLoS ONE 9(1):e83400PubMedPubMedCentralCrossRef Pane M, Mazzone ES, Sormani MP, Messina S, Vita GL, Fanelli L et al (2014) 6 Minute walk test in Duchenne MD patients with different mutations: 12 month changes. PLoS ONE 9(1):e83400PubMedPubMedCentralCrossRef
38.
go back to reference van den Bergen JC, Ginjaar HB, Niks EH, Aartsma-Rus A, Verschuuren JJ (2014) Prolonged ambulation in Duchenne Patients with a mutation amenable to exon 44 skipping. J Neuromuscul Dis 1(1):91–94PubMedCrossRef van den Bergen JC, Ginjaar HB, Niks EH, Aartsma-Rus A, Verschuuren JJ (2014) Prolonged ambulation in Duchenne Patients with a mutation amenable to exon 44 skipping. J Neuromuscul Dis 1(1):91–94PubMedCrossRef
39.
go back to reference Winnard AV, Mendell JR, Prior TW, Florence J, Burghes AH (1995) Frameshift deletions of exons 3–7 and revertant fibers in Duchenne muscular dystrophy: mechanisms of dystrophin production. Am J Hum Genet 56(1):158–166PubMedPubMedCentral Winnard AV, Mendell JR, Prior TW, Florence J, Burghes AH (1995) Frameshift deletions of exons 3–7 and revertant fibers in Duchenne muscular dystrophy: mechanisms of dystrophin production. Am J Hum Genet 56(1):158–166PubMedPubMedCentral
40.
go back to reference Wagner KR, Kuntz NL, Koenig E, East L, Upadhyay S, Han B et al (2021) Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: a randomized, double-blind, placebo-controlled, dose-titration trial. Muscle Nerve 64(3):285–292PubMedPubMedCentralCrossRef Wagner KR, Kuntz NL, Koenig E, East L, Upadhyay S, Han B et al (2021) Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: a randomized, double-blind, placebo-controlled, dose-titration trial. Muscle Nerve 64(3):285–292PubMedPubMedCentralCrossRef
41.
go back to reference Flanigan KM, Ceco E, Lamar KM, Kaminoh Y, Dunn DM, Mendell JR et al (2013) LTBP4 genotype predicts age of ambulatory loss in Duchenne muscular dystrophy. Ann Neurol 73(4):481–488PubMedPubMedCentralCrossRef Flanigan KM, Ceco E, Lamar KM, Kaminoh Y, Dunn DM, Mendell JR et al (2013) LTBP4 genotype predicts age of ambulatory loss in Duchenne muscular dystrophy. Ann Neurol 73(4):481–488PubMedPubMedCentralCrossRef
42.
go back to reference Disset A, Bourgeois CF, Benmalek N, Claustres M, Stevenin J, Tuffery-Giraud S (2006) An exon skipping-associated nonsense mutation in the dystrophin gene uncovers a complex interplay between multiple antagonistic splicing elements. Hum Mol Genet 15(6):999–1013PubMedCrossRef Disset A, Bourgeois CF, Benmalek N, Claustres M, Stevenin J, Tuffery-Giraud S (2006) An exon skipping-associated nonsense mutation in the dystrophin gene uncovers a complex interplay between multiple antagonistic splicing elements. Hum Mol Genet 15(6):999–1013PubMedCrossRef
43.
go back to reference Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C et al (2007) Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene. Hum Mutat 28(2):183–195PubMedCrossRef Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C et al (2007) Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene. Hum Mutat 28(2):183–195PubMedCrossRef
44.
go back to reference van Essen AJ, Mulder IM, van der Vlies P, van der Hout AH, Buys CH, Hofstra RM et al (2003) Detection of point mutation in dystrophin gene reveals somatic and germline mosaicism in the mother of a patient with Duchenne muscular dystrophy. Am J Med Genet A 118A(3):296–298PubMedCrossRef van Essen AJ, Mulder IM, van der Vlies P, van der Hout AH, Buys CH, Hofstra RM et al (2003) Detection of point mutation in dystrophin gene reveals somatic and germline mosaicism in the mother of a patient with Duchenne muscular dystrophy. Am J Med Genet A 118A(3):296–298PubMedCrossRef
45.
go back to reference Smith TA, Yau SC, Bobrow M, Abbs SJ (1999) Identification and quantification of somatic mosaicism for a point mutation in a duchenne muscular dystrophy family. J Med Genet 36(4):313–315PubMedPubMedCentral Smith TA, Yau SC, Bobrow M, Abbs SJ (1999) Identification and quantification of somatic mosaicism for a point mutation in a duchenne muscular dystrophy family. J Med Genet 36(4):313–315PubMedPubMedCentral
46.
go back to reference Ganapathy A, Mishra A, Soni MR, Kumar P, Sadagopan M, Kanthi AV et al (2019) Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients. Neurol 266(8):1919–1926CrossRef Ganapathy A, Mishra A, Soni MR, Kumar P, Sadagopan M, Kanthi AV et al (2019) Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients. Neurol 266(8):1919–1926CrossRef
47.
go back to reference Bhattacharya S, Das A, Dasgupta R, Bagchi A (2014) Analyses of the presence of mutations in dystrophin protein to predict their relative influences in the onset of Duchenne muscular dystrophy. Cell Signal 26(12):2857–2864PubMedCrossRef Bhattacharya S, Das A, Dasgupta R, Bagchi A (2014) Analyses of the presence of mutations in dystrophin protein to predict their relative influences in the onset of Duchenne muscular dystrophy. Cell Signal 26(12):2857–2864PubMedCrossRef
48.
go back to reference Lee T, Takeshima Y, Kusunoki N, Awano H, Yagi M, Matsuo M et al (2014) Differences in carrier frequency between mothers of Duchenne and Becker muscular dystrophy patients. J Hum Genet 59(1):46–50PubMedCrossRef Lee T, Takeshima Y, Kusunoki N, Awano H, Yagi M, Matsuo M et al (2014) Differences in carrier frequency between mothers of Duchenne and Becker muscular dystrophy patients. J Hum Genet 59(1):46–50PubMedCrossRef
49.
go back to reference Kawamura J, Kato S, Ishihara T, Hiraishi Y, Kawashiro T (1997) Difference of new mutation rates in dystrophin gene between deletion and duplication mutation in Duchenne and Becker muscular dystrophy. Rinsho Shinkeigaku 37(3):212–217PubMed Kawamura J, Kato S, Ishihara T, Hiraishi Y, Kawashiro T (1997) Difference of new mutation rates in dystrophin gene between deletion and duplication mutation in Duchenne and Becker muscular dystrophy. Rinsho Shinkeigaku 37(3):212–217PubMed
50.
go back to reference Helderman-van den Enden AT, de Jong R, den Dunnen JT, Houwing-Duistermaat JJ, Kneppers AL, Ginjaar HB et al (2009) Recurrence risk due to germ line mosaicism: Duchenne and Becker muscular dystrophy. Clin Genet 75(5):465–472PubMedCrossRef Helderman-van den Enden AT, de Jong R, den Dunnen JT, Houwing-Duistermaat JJ, Kneppers AL, Ginjaar HB et al (2009) Recurrence risk due to germ line mosaicism: Duchenne and Becker muscular dystrophy. Clin Genet 75(5):465–472PubMedCrossRef
51.
go back to reference Magri F, Govoni A, D’Angelo MG, Del Bo R, Ghezzi S, Sandra G et al (2011) Genotype and phenotype characterization in a large dystrophinopathic cohort with extended follow-up. J Neurol 258(9):1610–1623PubMedCrossRef Magri F, Govoni A, D’Angelo MG, Del Bo R, Ghezzi S, Sandra G et al (2011) Genotype and phenotype characterization in a large dystrophinopathic cohort with extended follow-up. J Neurol 258(9):1610–1623PubMedCrossRef
52.
go back to reference Polavarapu K, Preethish-Kumar V, Sekar D, Vengalil S, Nashi S, Mahajan NP et al (2019) Mutation pattern in 606 duchenne muscular dystrophy children with a comparison between familial and non-familial forms: a study in an Indian large single-center cohort. J Neurol 266(9):2177–2185PubMedCrossRef Polavarapu K, Preethish-Kumar V, Sekar D, Vengalil S, Nashi S, Mahajan NP et al (2019) Mutation pattern in 606 duchenne muscular dystrophy children with a comparison between familial and non-familial forms: a study in an Indian large single-center cohort. J Neurol 266(9):2177–2185PubMedCrossRef
53.
go back to reference Ercan ES, Kandulu R, Uslu E, Ardic UA, Yazici KU, Basay BK et al (2013) Prevalence and diagnostic stability of ADHD and ODD in Turkish children: a 4-year longitudinal study. Child Adolesc Psychiatry Ment Health 7(1):30PubMedPubMedCentralCrossRef Ercan ES, Kandulu R, Uslu E, Ardic UA, Yazici KU, Basay BK et al (2013) Prevalence and diagnostic stability of ADHD and ODD in Turkish children: a 4-year longitudinal study. Child Adolesc Psychiatry Ment Health 7(1):30PubMedPubMedCentralCrossRef
54.
go back to reference Pane M, Lombardo ME, Alfieri P, D’Amico A, Bianco F, Vasco G et al (2012) Attention deficit hyperactivity disorder and cognitive function in Duchenne muscular dystrophy: phenotype-genotype correlation. J Pediatr 161(4):705–9e1PubMedCrossRef Pane M, Lombardo ME, Alfieri P, D’Amico A, Bianco F, Vasco G et al (2012) Attention deficit hyperactivity disorder and cognitive function in Duchenne muscular dystrophy: phenotype-genotype correlation. J Pediatr 161(4):705–9e1PubMedCrossRef
55.
go back to reference Hendriksen JG, Vles JS (2008) Neuropsychiatric disorders in males with duchenne muscular dystrophy: frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive–compulsive disorder. J Child Neurol 23(5):477–481PubMedCrossRef Hendriksen JG, Vles JS (2008) Neuropsychiatric disorders in males with duchenne muscular dystrophy: frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive–compulsive disorder. J Child Neurol 23(5):477–481PubMedCrossRef
Metadata
Title
Investigation of genotype-phenotype and familial features of Turkish dystrophinopathy patients
Authors
Hande Ozkalayci
Elcin Bora
Tufan Cankaya
Mehmet Kocabey
Nadide Cemre Zubari
Uluc Yis
Ozlem Giray Bozkaya
Serkan Turan
Aynur Pekcanlar Akay
Ahmet Okay Caglayan
Ayfer Ulgenalp
Publication date
08-06-2024
Publisher
Springer Berlin Heidelberg
Published in
Neurogenetics
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI
https://doi.org/10.1007/s10048-024-00765-9