A novel phenotype of 13q12.3 microdeletion characterized by epilepsy in an Asian child: a case report

BMC Medical Genomics - Tập 13 Số 1 - 2020
Mina Wang1, Bin Li1, Ziqi Liao2, Yu Ji3, Yuanbo Fu1
1The Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, 100010, China
2School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
3Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China

Tóm tắt

Abstract Background The microdeletion of chromosome 13 has been rarely reported. Here, we report a 14-year old Asian female with a de novo microdeletion on 13q12.3. Case presentation The child suffered mainly from two types of epileptic seizures: partial onset seizures and myoclonic seizures, accompanied with intellectual disability, developmental delay and minor dysmorphic features. The electroencephalogram disclosed slow waves in bilateral temporal, together with generalized spike-and-slow waves, multiple-spike-and-slow waves and slow waves in bilateral occipitotemporal regions. The exome sequencing showed no pathogenic genetic variation in the patient’s DNA sample. While the single nucleotide polymorphism (SNP) array analysis revealed a de novo microdeletion spanning 2.324 Mb, within the cytogenetic band 13q12.3. Conclusions The epilepsy may be associated with the mutation of KATNAL1 gene or the deletion unmasking a recessive mutation on the other allele, and our findings could provide a phenotypic expansion.

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Tài liệu tham khảo

McTague A, Howell KB, Cross JH, Kurian MA, Scheffer IE. The genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol. 2016;15(3):304–16.

Hussain SA. Epileptic Encephalopathies. Continuum (Minneap Minn). 2018;24(1, Child Neurology):171–85.

Guerreiro CA. Epilepsy: is there hope? Indian J Med Res. 2016;144(5):657–60.

Bartholdi D, Stray-Pedersen A, Azzarello-Burri S, Kibaek M, Kirchhoff M, Oneda B, et al. A newly recognized 13q12.3 microdeletion syndrome characterized by intellectual disability, microcephaly, and eczema/atopic dermatitis encompassing the HMGB1 and KATNAL1 genes. Am J Med Genet A. 2014;164A(5):1277–83.

Drummond-Borg M, Kulharya AS, Tonk V, Garcia-Heras J. Maternal complex chromosome rearrangement ascertained through a del (13)(q12.1q14.1) detected in her mildly affected daughter. Am J Med Genet. 2002;107(1):61–3.

Ballarati L, Rossi E, Bonati MT, Gimelli S, Maraschio P, Finelli P, et al. 13q deletion and central nervous system anomalies: further insights from karyotype-phenotype analyses of 14 patients. J Med Genet. 2007;44(1):e60.

Der Kaloustian VM, Russell L, Aradhya S, Richard G, Rosenblatt B, Melançon S. A de novo 2.1-Mb deletion of 13q12.11 in a child with developmental delay and minor dysmorphic features. Am J Med Genet A. 2011;155A(10):2538–42.

Cirillo E, Romano R, Romano A, Giardino G, Durandy A, Nitsch L, et al. De novo 13q12.3-q14.11 deletion involving BRCA2 gene in a patient with developmental delay, elevated IgM levels, transient ataxia, and cerebellar hypoplasia, mimicking an A-T like phenotype. Am J Med Genet A. 2012;158A(10):2571–6.

Du Puy L, Beqqali A, Monshouwer-Kloots J, Haagsman HP, Roelen BAJ, Passier R. CAZIP, a novel protein expressed in the developing heart and nervous system. Dev Dyn. 2009;238(11):2903–11.

Yang Z, Kaye DM. Mechanistic insights into the link between a polymorphism of the 3'UTR of the SLC7A1 gene and hypertension. Hum Mutat. 2009;30(3):328–33.

Wang Y. Jin L: miRNA-145 is associated with spontaneous hypertension by targeting SLC7A1. Exp Ther Med. 2018;15(1):548–52.

Hatakeyama E, Hayashi K. KATNAL1 is a more active and stable isoform of katanin, and is expressed dominantly in neurons. Biochem Biophys Res Commun. 2018;507(1–4):389–94.

Banks G, Lassi G, Hoerder-Suabedissen A, Tinarelli F, Simon MM, Wilcox A, et al. A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies. Mol Psychiatry. 2018;23(3):713–22.

Maroso M, Balosso S, Ravizza T, Liu J, Aronica E, Iyer AM, et al. Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat Med. 2010;16(4):413–9.

Shi Y, Zhang L, Teng J, Miao W. HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy. Mol Med Rep. 2018;17(4):5125–31.

Yang W, Li J, Shang Y, Zhao L, Wang M, Shi J, et al. HMGB1-TLR4 Axis plays a regulatory role in the pathogenesis of mesial temporal lobe epilepsy in immature rat model and children via the p38MAPK signaling pathway. Neurochem Res. 2017;42(4):1179–90.

Bermejo JL, Kabisch M, Dünnebier T, Schnaidt S, Melchior F, Fischer HP, et al. Exploring the association between genetic variation in the SUMO isopeptidase gene USPL1 and breast cancer through integration of data from the population-based GENICA study and external genetic databases. Int J Cancer. 2013;133(2):362–72.

Schulz S, Chachami G, Kozaczkiewicz L, Winter U, Stankovic-Valentin N, Haas P, et al. Ubiquitin-specific protease-like 1 (USPL1) is a SUMO isopeptidase with essential, non-catalytic functions. EMBO Rep. 2012;13(10):930–8.

Evans JF, Ferguson AD, Mosley RT, Hutchinson JH. What's all the FLAP about?: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases. Trends Pharmacol Sci. 2008;29(2):72–8.

Al-Shemari H, Bossé Y, Hudson TJ, Cabaluna M, Duval M, Lemire M, et al. Influence of leukotriene gene polymorphisms on chronic rhinosinusitis. BMC Med Genet. 2008;9:21.

Toyo-Oka K, Sasaki S, Yano Y, Mori D, Kobayashi T, Toyoshima YY, et al. Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration. Hum Mol Genet. 2005;14(21):3113–28.

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BMC Medical Genomics

Tập 13 Số 1

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