ExpandedDMPKrepeats in dizygotic twins referred for diagnosis of autism versus absence of expandedDMPKrepeats at screening of 330 children with autism.
Myotonic dystrophy type 1 (DM1) belongs to the broad spectrum of genetic disorders associated with autism spectrum disorders (ASD). ASD were reported predominantly in congenital and early childhood forms of DM1. We describe dizygotic twin boys with ASD who were referred for routine laboratory genetic testing and in whom karyotyping,FMR1gene testing, and single nucleotide polymorphism array analysis yielded negative results. The father of the boys was later diagnosed with suspected DM1, and testing revealed characteristicDMPKgene expansions in his genome as well as in the genomes of both twins and their elder brother, who also suffered from ASD. In accord with previous reports on childhood forms of DM1, our patients showed prominent neuropsychiatric phenotypes characterized especially by hypotonia, developmental and language delay, emotional and affective lability, lowered adaptability, and social withdrawal. The experience with this family and multiple literature reports of ASD in DM1 on the one side but the lack of literature data on the frequency ofDMPKgene expansions in ASD patients on the other side prompted us to screen theDMPKgene in a sample of 330 patients with ASD who were first seen by a geneticist before they were 10 years of age, before the muscular weakness, which may signal DM1, usually becomes obvious. The absence of anyDMPKgene expansions in this cohort indicates that targetedDMPKgene testing can be recommended only in ASD patients with specific symptoms or family history suggestive of DM1.
Department of Biology and Medical Genetics.
Zuzana
Z
Musova
Department of Biology and Medical Genetics.
Miroslava
M
Hancarova
Department of Biology and Medical Genetics.
Marketa
M
Havlovicova
Department of Biology and Medical Genetics.
Radka
R
Pourova
Department of Child Psychiatry.
Michal
M
Hrdlicka
Department of Child Neurology, Charles University 2nd Faculty of Medicine and University Hospital Motol.
Josef
J
Kraus
Gennet, Centre for Fetal Medicine, Prague, Czech Republic.
Marie
M
Trkova
Gennet, Centre for Fetal Medicine, Prague, Czech Republic.
David
D
Stejskal
Department of Biology and Medical Genetics.
Zdenek
Z
Sedlacek
DMPK gene; autism; comorbidity; genetic testing; myotonic dystrophy type 1
World J Clin Pediatr. 2015 Nov 08;4(4):66-80
26566479
Handb Clin Neurol. 2013;113:1387-93
23622362
PLoS One. 2013 Sep 05;8(9):e72907
24039817
Am J Med Genet A. 2009 Jul;149A(7):1365-74
19514047
J Mol Diagn. 2005 Nov;7(5):605-12
16258159
Dev Med Child Neurol. 1996 Sep;38(9):840-7
8810716
Dev Med Child Neurol. 1997 Apr;39(4):280-1
9183272
Eur J Hum Genet. 2012 Dec;20(12):1203-8
22643181
Am J Hum Genet. 1993 Jun;52(6):1164-74
8503448
J Med Genet. 1996 Dec;33(12):1022-6
9004136
Acta Neurol Scand. 2007 Apr;115(4):265-70
17376125
Pediatr Clin North Am. 2012 Feb;59(1):113-28, xi
22284797
Front Genet. 2014 Apr 10;5:81
24782891
Hum Mol Genet. 2015 Oct 15;24(R1):R24-31
26188008
No To Hattatsu. 1989 Jul;21(4):379-84
2789860
Am J Med Genet B Neuropsychiatr Genet. 2013 Jun;162B(4):327-66
23650212
Am J Med Genet. 2000 Dec 4;96(6):888-9
11121206
Eur J Paediatr Neurol. 2008 May;12(3):210-23
17892958
Clin Genet. 1997 Sep;52(3):135-41
9377801
Am J Med Genet B Neuropsychiatr Genet. 2008 Sep 5;147B(6):918-26
18228241
Dev Med Child Neurol. 2012 Oct;54(10):905-11
22861906