A DMD case caused by X chromosome rearrangement
Received date: 2022-09-26
Revised date: 2022-11-16
Online published: 2022-12-12
Supported by
Hunan Innovative Province Construction Special Fund(2019SK4012);the Health and Livelihood Project of Changsha(Comprehensive Prevention);the Health and Livelihood Project of Changsha(Control of Inherited Rare Disorders)
Duchenne/Becker muscular dystrophy (DMD/BMD) is one of the most common progressive muscular dystrophy diseases with X-linked recessive inheritance. It is mainly caused by the deletion, duplication and point mutation of DMD gene. In rare cases, it is also caused by the destruction of DMD gene by chromosomal structural rearrangement. Here, we report a case of Duchenne/Becker Muscular dystrophy (DMD/BMD) with typical symptoms but unknown genetic defects after MLPA and next generation sequencing tests in other hospitals. Interestingly, we find a pericentric inversion of X chromosome (Chr.X: g. [31939463-31939465del; 31939466-131765063 inv; 131765064-131765067del]) in this patient. We then use the karyotyping, FISH, long-read sequencing and Sanger sequencing technologies to characterize the chromosome rearrangement. We find that this chromosomal aberration disrupt both the DMD gene and the HS6ST2 gene. The patient present with typical DMD symptoms such as muscle weakness, but no obvious symptoms of Paganini-Miozzo syndrome. Our results suggest that the destruction of DMD gene by structural rearrangement is also one of the important causes of DMD. Therefore, we suggest to provide further genetic testing for those DMD patients with unknown genetic defects through routine genetic testing. Cost-effective karyotyping and FISH should be considered firstly to identify chromosome rearrangements. Long-read sequencing followed by Sanger sequencing could be useful to locate the precise breakpoints. The genetic diagnosis of this case made it possible for reproductive intervention in the patient’s family.
Key words： DMD; structural rearrangement; karyotype; FISH; breakpoint analysis
Hao Hu, Xiaowen Yang, Dehua Cheng, Xiurong Li, Wenbin He, Xiao Hu, Bodi Gao, Xiaomeng Zhao, Qianjun Zhang, Juan Du, Jiyang Liu, Guangxiu Lu, Lin Ge, Wen Li . A DMD case caused by X chromosome rearrangement[J]. Hereditas(Beijing), 2023 , 45(1) : 88 -95 . DOI: 10.16288/j.yczz.22-179
| [1] | Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K, Kosma K, Dawkins H, Lamont L, Roy AJ, Chamova T, Guergueltcheva V, Chan S, Korngut L, Campbell C, Dai Y, Wang J, Barišić N, Brabec P, Lahdetie J, Walter MC, Schreiber-Katz O, Karcagi V, Garami M, Viswanathan V, Bayat F, Buccella F, Kimura E, Koeks Z, van den Bergen JC, Rodrigues M, Roxburgh R, Lusakowska A, Kostera- Pruszczyk A, Zimowski J, Santos R, Neagu E, Artemieva S, Rasic VM, Vojinovic D, Posada M, Bloetzer C, Jeannet PY, Joncourt F, Díaz-Manera J, Gallardo E, Karaduman AA, Topaloğlu H, Sherif RE, Stringer A, Shatillo AV, Martin AS, Peay HL, Bellgard MI, Kirschner J, Flanigan KM, Straub V, Bushby K, Verschuuren J, Aartsma-Rus A, Béroud C, Lochmüller H. The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum Mutat, 2015, 36(4): 395-402. |
| [2] | Kong XD, Zhong XJ, Liu LN, Cui SY, Yang YX, Kong LR. Genetic analysis of 1051 Chinese families with Duchenne/ Becker Muscular Dystrophy. BMC Med Genet, 2019, 20(1): 139. |
| [3] | Crisafulli S, Sultana J, Fontana A, Salvo F, Messina S, Trifirò G. Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta- analysis. Orphanet J Rare Dis, 2020, 15(1): 141. |
| [4] | Human Genome Mutation DatabaseHGMD[2022-08-01].https://my.qiagendigitalinsights.com/bbp/view/hgmd/pro/start.php. |
| [5] | Shashi V, Golden WL, Allinson PS, Blanton SH, von Kap- Herr C, Kelly TE. Molecular analysis of recombination in a family with Duchenne muscular dystrophy and a large pericentric X chromosome inversion. Am J Hum Genet, 1996, 58(6): 1231-1238. |
| [6] | Saito-Ohara F, Fukuda Y, Ito M, Agarwala KL, Hayashi M, Matsuo M, Imoto I, Yamakawa K, Nakamura Y, Inazawa J. The Xq 22 inversion breakpoint interrupted a novel Ras-like GTPase gene in a patient with Duchenne muscular dystrophy and profound mental retardation. Am J Hum Genet, 2002, 71(3): 637-645. |
| [7] | Bhat SS, Schmidt KR, Ladd S, Kim KC, Schwartz CE, Simensen RJ, DuPont BR, Stevenson RE, Srivastava AK. Disruption of DMD and deletion of ACSL4 causing developmental delay, hypotonia, and multiple congenital anomalies. Cytogenet Genome Res, 2006, 112(1-2): 170-175. |
| [8] | Kawashima H, Watanabe K, Morishima Y, Ioi H, Kashiwagi Y, Miyajima T, Takekuma K, Nishino I, Numabe H. High concentration of middle chain fatty acid in a case of Duchenne muscular dystrophy with severe mental retardation. Pediatr Int, 2012, 54(1): 137-140. |
| [9] | Tran THT, Zhang ZJ, Yagi M, Lee T, Awano H, Nishida A, Okinaga T, Takeshima Y, Matsuo M.Molecular characterization of an X(p21.2;q28) chromosomal inversion in a Duchenne muscular dystrophy patient with mental retardation reveals a novel long non-coding gene on Xq28. J Hum Genet, 2013, 58(1): 33-39. |
| [10] | Habuchi H, Miyake G, Nogami K, Kuroiwa A, Matsuda Y, Kusche-Gullberg M, Habuchi O, Tanaka M, Kimata K. Biosynthesis of heparan sulphate with diverse structures and functions: two alternatively spliced forms of human heparan sulphate 6-O-sulphotransferase-2 having different expression patterns and properties. Biochem J, 2003, 371(Pt 1): 131-142. |
| [11] | Habuchi H, Tanaka M, Habuchi O, Yoshida K, Suzuki H, Ban K, Kimata K. The occurrence of three isoforms of heparan sulfate 6-O-sulfotransferase having different specificities for hexuronic acid adjacent to the targeted N-sulfoglucosamine. J Biol Chem, 2000, 275(4): 2859- 2868. |
| [12] | Paganini L, Hadi LA, Chetta M, Rovina D, Fontana L, Colapietro P, Bonaparte E, Pezzani L, Marchisio P, Tabano SM, Costanza J, Sirchia SM, Riboni L, Milani D, Miozzo M. A HS6ST2 gene variant associated with X-linked intellectual disability and severe myopia in two male twins. Clin Genet, 2019, 95(3): 368-374. |
/
| 〈 |
|
〉 |
www.chinagene.cn
备案号：京ICP备09063187号
