Bi-allelic loss of function variants in SLC30A5 as cause of perinatal lethal cardiomyopathy.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
30
09
2020
accepted:
17
12
2020
revised:
13
12
2020
pubmed:
7
2
2021
medline:
18
1
2022
entrez:
6
2
2021
Statut:
ppublish
Résumé
Perinatal mortality is a heavy burden for both affected parents and physicians. However, the underlying genetic causes have not been sufficiently investigated and most cases remain without diagnosis. This impedes appropriate counseling or therapy. We describe four affected children of two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. In the four patients, we found the following homozygous loss of function (LoF) variants in SLC30A5 NM_022902.4:c.832_836del p.(Ile278Phefs*33) and NM_022902.4:c.1981_1982del p.(His661Tyrfs*10). Knockout of SLC30A5 has previously been shown a cardiac phenotype in mouse models and no homozygous LoF variants in SLC30A5 are currently described in gnomAD. Taken together, we present SLC30A5 as a new gene for a severe and perinatally lethal form of cardiomyopathy.
Identifiants
pubmed: 33547425
doi: 10.1038/s41431-020-00803-8
pii: 10.1038/s41431-020-00803-8
pmc: PMC8110774
doi:
Substances chimiques
Cation Transport Proteins
0
SLC30A5 protein, human
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
808-815Commentaires et corrections
Type : ErratumIn
Références
Oster RT, Toth EL, Retrospective A. Analysis of stillbirth epidemiology and risk factors among First Nations and non-First Nations Pregnancies in Alberta from 2000 to 2009. J Obstet Gynaecol Can. 2015;37:117–21.
doi: 10.1016/S1701-2163(15)30332-7
Blencowe H, Cousens S, Jassir FB, Say L, Chou D, Mathers C, et al. National, regional, and worldwide estimates of stillbirth rates in 2015, with trends from 2000: a systematic analysis. Lacent Glob Health. 2016;4:e98–108.
doi: 10.1016/S2214-109X(15)00275-2
McClure EM, Nalubamba-Phiri M, Goldenberg RL. Stillbirth in developing countries. Int J Gynaecol Obstet. 2006;94:82–90.
doi: 10.1016/j.ijgo.2006.03.023
Aminu M, Unkels R, Mdegela M, Utz B, Adaji S, van den Broek N. Causes of and factors associated with stillbirth in low- and middle-income countries: a systematic literature review. BJOG. 2014;121 Suppl 4:141–53.
doi: 10.1111/1471-0528.12995
McPherson E. Hydrops fetalis in a cohort of 3,137 stillbirths and second trimester miscarriages. Am J Med Genet Part A. 2019;179:2338–42.
doi: 10.1002/ajmg.a.61340
Mardy AH, Chetty SP, Norton ME, Sparks TN. A system-based approach to the genetic etiologies of non-immune hydrops fetalis. Prenat Diagn. 2019;39:732–50.
doi: 10.1002/pd.5479
Santo S, Mansour S, Thilaganathan B, Homfray T, Papageorghiou A, Calvert S, et al. Prenatal diagnosis of non-immune hydrops fetalis: what do we tell the parents? Prenat Diagn. 2011;31:186–95.
doi: 10.1002/pd.2677
Bellini C, Donarini G, Paladini D, Calevo MG, Bellini T, Ramenghi LA, et al. Etiology of non-immune hydrops fetalis: an update. Am J Med Genet A. 2015;167A:1082–8.
doi: 10.1002/ajmg.a.36988
Sparks TN, Thao K, Lianoglou BR, Boe NM, Bruce KG, Datkhaeva I, et al. Nonimmune hydrops fetalis: identifying the underlying genetic etiology. Genet Med. 2019;21:1339–44.
doi: 10.1038/s41436-018-0352-6
Lord J, McMullan DJ, Eberhardt RY, Rinck G, Hamilton SJ, Quinlan-Jones E, et al. Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study. Lancet. 2019;393:747–57.
doi: 10.1016/S0140-6736(18)31940-8
Petrovski S, Aggarwal V, Giordano JL, Stosic M, Wou K, Bier L, et al. Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study. Lancet. 2019;393:758–67.
doi: 10.1016/S0140-6736(18)32042-7
Sobreira N, Schiettecatte F, Valle D, Hamosh A. GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum Mutat. 2015;36:928–30.
doi: 10.1002/humu.22844
Landrum MJ, Lee JM, Benson M, Brown GR, Chao C, Chitipiralla S, et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018;46:D1062–7.
doi: 10.1093/nar/gkx1153
Stenson PD, Mort M, Ball EV, Evans K, Hayden M, Heywood S, et al. The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. Hum Genet. 2017;136:665–77.
doi: 10.1007/s00439-017-1779-6
Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581:434–43.
doi: 10.1038/s41586-020-2308-7
Voigt M, Fusch C, Olbertz D, Hartmann K, Rochow N, Renken C, et al. Analyse des Neugeborenenkollektivs der Bundesrepublik Deutschland. Geburtsh Frauenheilk. 2006;66:956–70.
doi: 10.1055/s-2006-924458
Vallee BL, Falchuk KH. The biochemical basis of zinc physiology. Physiological Rev. 1993;73:79–118.
doi: 10.1152/physrev.1993.73.1.79
Kambe T, Matsunaga M, Takeda T-A. Understanding the contribution of zinc transporters in the function of the early secretory pathway. Int J Mol Sci. 2017;18:2179.
doi: 10.3390/ijms18102179
Hennigar SR, Kelleher SL. Zinc networks: the cell-specific compartmentalization of zinc for specialized functions. Biol Chem. 2012;393:565–78.
doi: 10.1515/hsz-2012-0128
Costello LC, Franklin RB, Feng P. Mitochondrial function, zinc, and intermediary metabolism relationships in normal prostate and prostate cancer. Mitochondrion. 2005;5:143–53.
doi: 10.1016/j.mito.2005.02.001
Fukunaka A, Suzuki T, Kurokawa Y, Yamazaki T, Fujiwara N, Ishihara K, et al. Demonstration and characterization of the heterodimerization of ZnT5 and ZnT6 in the early secretory pathway. J Biol Chem. 2009;284:30798–806.
doi: 10.1074/jbc.M109.026435
Oteiza PI, Hurley LS, Lönnerdal B, Keen CL. Effects of marginal zinc deficiency on microtubule polymerization in the developing rat brain. Biol Trace Elem Res. 1990;24:13–23.
doi: 10.1007/BF02789137
Yamasaki S, Sakata-Sogawa K, Hasegawa A, Suzuki T, Kabu K, Sato E, et al. Zinc is a novel intracellular second messenger. J Cell Biol. 2007;177:637–45.
doi: 10.1083/jcb.200702081
Sekler I, Sensi SL, Hershfinkel M, Silverman WF. Mechanism and regulation of cellular zinc transport. Mol Med. 2007;13:337–43.
doi: 10.2119/2007-00037.Sekler
Tuschl K, Clayton PT, Gospe SM, Gulab S, Ibrahim S, Singhi P, et al. Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. Am J Hum Genet. 2012;90:457–66.
doi: 10.1016/j.ajhg.2012.01.018
Chowanadisai W, Lönnerdal B, Kelleher SL. Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. J Biol Chem. 2006;281:39699–707.
doi: 10.1074/jbc.M605821200
Kumar L, Michalczyk A, McKay J, Ford D, Kambe T, Hudek L, et al. Altered expression of two zinc transporters, SLC30A5 and SLC30A6, underlies a mammary gland disorder of reduced zinc secretion into milk. Genes Nutr. 2015;10:487.
doi: 10.1007/s12263-015-0487-x
Küry S, Dréno B, Bézieau S, Giraudet S, Kharfi M, Kamoun R, et al. Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet. 2002;31:239–40.
doi: 10.1038/ng913
Boycott KM, Beaulieu CL, Kernohan KD, Gebril OH, Mhanni A, Chudley AE, et al. Autosomal-recessive intellectual disability with cerebellar atrophy syndrome caused by mutation of the manganese and zinc transporter gene SLC39A8. Am J Hum Genet. 2015;97:886–93.
doi: 10.1016/j.ajhg.2015.11.002
Giunta C, Elçioglu NH, Albrecht B, Eich G, Chambaz C, Janecke AR, et al. Spondylocheiro dysplastic form of the Ehlers-Danlos syndrome—an autosomal-recessive entity caused by mutations in the zinc transporter gene SLC39A13. Am J Hum Genet. 2008;82:1290–305.
doi: 10.1016/j.ajhg.2008.05.001
Tuschl K, Meyer E, Valdivia LE, Zhao N, Dadswell C, Abdul-Sada A, et al. Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia. Nat Commun. 2016;7:11601.
doi: 10.1038/ncomms11601
Guo H, Jin X, Zhu T, Wang T, Tong P, Tian L, et al. SLC39A5 mutations interfering with the BMP/TGF-β pathway in non-syndromic high myopia. J Med Genet. 2014;51:518–25.
doi: 10.1136/jmedgenet-2014-102351
Lin W, Li D, Cheng L, Li L, Liu F, Hand NJ, et al. Zinc transporter Slc39a8 is essential for cardiac ventricular compaction. J Clin Investig. 2018;128:826–33.
doi: 10.1172/JCI96993
Inoue K, Matsuda K, Itoh M, Kawaguchi H, Tomoike H, Aoyagi T, et al. Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5. Hum Mol Genet. 2002;11:1775–84.
doi: 10.1093/hmg/11.15.1775
McCoy MC, Katz VL, Gould N, Kuller JA. Non-immune hydrops after 20 weeks’ gestation: review of 10 years’ experience with suggestions for management. Obstet Gynecol. 1995;85:578–82.
doi: 10.1016/0029-7844(94)00312-2