377:(MR) in her family history, but had slight hypotonia. Patient three was the oldest at 36 who began to walk at age 3. She later gained weight at eleven and developed epilepsy in her late twenties. The fourth patient had problems associated with eating as a young child and was diagnosed with slowed development. Patient five had behavioural issues and struggled with MR in addition to being overweight. The geneticists discovered three new mutations within the EHMT1 gene. The first was an interstitial deletion, while the second and third were a nonsense and frameshift. Their findings supported the notion that a disruption in the EHMT1 gene contributes to the pathogenesis of Kleefstra syndrome.
334:
tumours in the glial cells of the brain, as well as chromosomal abnormalities. Array-based comparative genomic hybridization (aCGH) tracks chromosome deletions and or amplifications using fluorescent dyes on genomic sequences of DNA samples. The DNA samples (which are 25-80 base pairs in length) are then placed on slides to be observed under microscope. Lastly, EHMT1 sequencing is a process in which a single-strand of DNA from the EHMT1 gene is removed, and DNA polymerase is added in order to synthesize complementary strands. In turn, this allows scientists to map out a person's DNA sequence allowing for a diagnosis to be made.
384:, DNA from forty patients were extracted and subjected to MLPA, FISH or EHMT1 sequencing. The forty patients were divided into two groups: 1 group of 16 patients with the 9q34 deletion, and 1 group of 24 with typical FISH/MPLA results. The geneticists examined how a missense mutation would affect the function of the DNA by looking at DNA models. After, they screened each person's DNA using one of three tests, the results for the first group showed six patients had the same deletion of the same size (700 kb). In the second group, after EHMT1 sequencing was performed, six
61:
37:
434:
Willemsen MH, Vulto-van
Silfhout AT, Nillesen WM, Wissink-Lindhout WM, van Bokhoven H, Philip N, Berry-Kravis EM, Kini U, van Ravenswaaij-Arts CM, Delle Chiaie B, Innes AM, Houge G, Kosonen T, Cremer K, Fannemel M, Stray-Pedersen A, Reardon W, Ignatius J, Lachlan K, Mircher C, Helderman van den Enden
305:
In the past, research showed that the austerity of the disease was directly proportional to the number of EHMT1 deletions prevalent in an individual. The greater the deletions, the greater the severity of the condition. However, in recent studies, 9q34 deletion syndrome occurs when the EHMT1 gene is
871:
Kleefstra, T; van Zelst-Stams, W A; Nillesen, W M; Cormier-Daire, V; Houge, G; Foulds, N; van Dooren, M; Willemsen, M H; Pfundt, R; Turner, A; Wilson, M; McGaughran, J; Rauch, A; Zenker, M; Adam, M P; Innes, M; Davies, C; Lopez, A G.-M.; Casalone, R; Weber, A; Brueton, L A; Navarro, A D.; Bralo, M
350:
Kleefstra syndrome affects males and females equally and approximately 75% of all documented cases are caused by Eu-HMTase1 disruptions while only 25% are caused by 9q34.3 deletions. There are no statistics on the effect the disease has on life expectancy due to the lack of information available.
333:
to find any chromosome irregularities in a genome. It can be used for gene mapping, detecting aneuploidy, locating tumours etc. The multicolour probes attach to a certain DNA fragment. MLPA is a test that finds and records DNA copy change numbers through the use of PCR. MLPA can be used to detect
372:
performed an EHMT1 mutation analysis on 23 patients that showed symptoms of 9q34 deletion syndrome. The patients all varied in age. With respect to all the analyses, however, the clinical data focused on five patients, the majority being children. The first patient developed epilepsy early on in
821:
Kleefstra, Tjitske; Brunner, Han G.; Amiel, Jeanne; Oudakker, Astrid R.; Nillesen, Willy M.; Magee, Alex; Geneviève, David; Cormier-Daire, Valérie; van Esch, Hilde; Fryns, Jean-Pierre; Hamel, Ben C.J.; Sistermans, Erik A.; de Vries, Bert B.A.; van
Bokhoven, Hans (August 2006).
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969:
954:
285:
In the exception case, the mother transferred the EHMT1 point mutation on to her child as she was a carrier of this gene defect. According to Mitter, et al. (2012), the mother's phenotype of the NM_024757.4:c.2712+1G>A mutation displayed
388:
mutations were discovered. The scientists investigating this experiment conclude these mutations may be infective agents for the disease. Lastly, the patients' behavioural, physical, and psychiatric symptoms are included on the data chart.
359:
Kleefstra syndrome is a new condition that has only been known about for a few years and there have been fewer than 200 cases, reported. Due to the lack of cases worldwide, the history behind the origination is unclear.
290:
at certain tissues. This mutation resulted in the disregard of exon 18 on the EHMT1 gene, as opposed to removing it through the spliceosomes. In another transcript, however, an
175:, prominent jaw and a pouting lower lip. Individuals with this disease may often have speech impediments, such as speech delays. Other characteristics of this disease include:
779:
191:
which functions to alter histones. Ultimately, histone methyltransferases are important in deactivating certain genes, needed for proper growth and development. Moreover, a
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319:
183:, corpulence, and psychiatric disorders. From analysis of chromosomal breakpoints, as well as gene sequencing in suggestive cases, Kleefstra and colleagues identified
100:
874:"Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of EHMT1 haploinsufficiency to the core phenotype"
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1126:
373:
childhood, and had speech problems past age 8. He had hypoplasia and had prominent facial features, such as lips and mouth. The second patient had no trace of
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Despite the associated effects of
Kleefstra, there is insubstantial information regarding to the lethality of Kleefstra's. Most of the documented cases are
1116:
1067:
323:
104:
1141:
1136:
999:
560:"Disruption of the gene Euchromatin Histone Methyl Transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome"
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315:
96:
634:"A mosaic maternal splice donor mutation in the EHMT1 gene leads to aberrant transcripts and to Kleefstra syndrome in the offspring"
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776:
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482:
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824:"Loss-of-Function Mutations in Euchromatin Histone Methyl Transferase 1 (EHMT1) Cause the 9q34 Subtelomeric Deletion Syndrome"
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489:
381:
683:"Applications of fluorescence in situ hybridization (FISH) in detecting genetic aberrations of medical significance"
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Jeuken, Judith; Cornelissen, Sandra; Boots-Sprenger, Sandra; Gijsen, Sabine; Wesseling, Pieter (September 2006).
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188:
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195:, missense, or nonsense error in the coding sequence of EHMT1 can result in this condition in an individual.
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129:
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was placed between exon 18 and 19 of the EHMT1 gene. The combination of the intron insertion and the
171:. The facial features typically described include arched eyebrows, small head circumference, midface
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988:
192:
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with the exception of one case due to hereditary factors; however, some cases may be a result of
69:
1021:
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P.; Venselaar, H; Stegmann, S P A; Yntema, H G; van
Bokhoven, H; Brunner, H G (4 March 2009).
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Rump, A; Hildebrand, L; Tzschach, A; Ullmann, R; Schrock, E; Mitter, D (August 2013).
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PT, Mastebroek M, Cohn-Hokke PE, Yntema HG, Drunat S, Kleefstra T (2012).
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as the causative gene. This gene is responsible for producing the protein
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9q34.3 deletion syndrome is inherited in an autosomal dominant fashion.
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Tests are either conducted at birth, or later in early childhood via:
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Individual manifestations are treated by a multidisciplinary team.
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764:"HOW DOES ARRAY-BASED COMPARATIVE GENOMIC HYBRIDIZATION WORK?"
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in the mother was transferred to the child, resulting in the
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FISH is a screening test that uses multicolour probes or
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74:Arched eyebrows, small head circumference, midface
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48:
26:
21:
716:"Multiplex Ligation-Dependent Probe Amplification"
524:Kleefstra T, Nillesen WM, Yntema HG (7 May 2015).
306:non-functioning, as opposed to strictly deletion.
320:multiplex ligation-dependent probe amplification
101:multiplex ligation-dependent probe amplification
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1132:Syndromes with craniofacial abnormalities
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488:Rare Chromosome Disorder Support Group,
78:, prominent jaw and a pouting lower lip.
762:Peng, H.H., & Van den Veyyer, I.B.
423:
324:array comparative genomic hybridization
163:34 have been associated with childhood
105:array comparative genomic hybridization
1127:Syndromes with intellectual disability
828:The American Journal of Human Genetics
167:, a distinctive facial appearance and
179:, congenital and urogenital defects,
7:
720:The Journal of Molecular Diagnostics
230:Severe delay or total lack of speech
926:The Genetics Home Reference website
1117:Autosomal monosomies and deletions
638:European Journal of Human Genetics
380:In another study published by the
370:American Journal of Human Genetics
316:fluorescence in situ hybridization
97:Fluorescence in situ hybridization
14:
331:comparative genomic hybridization
412:Kleefstra Syndrome Worldwide Map
681:Bishop, R. (27 February 2010).
777:"Principles of DNA Sequencing"
437:"Update on Kleefstra Syndrome"
326:(aCGH), and EHMT1 sequencing.
136:, and MBD5 haploinsufficiency.
1:
797:"What is Kleefstra syndrome?"
1142:Syndromes with microcephaly
1137:Syndromes affecting the jaw
1073:Syndrome Kleefstra Syndrome
878:Journal of Medical Genetics
564:Journal of Medical Genetics
382:Journal of Medical Genetics
1158:
932:Boston Children's Hospital
732:10.2353/jmoldx.2006.060012
700:10.1093/biohorizons/hzq009
280:chromosomal translocations
236:Dysmorphic facial features
215:Genital defects (in males)
368:A study published by the
263:Disliking routine changes
212:Characteristics of autism
189:histone methyltransferase
43:
34:
169:developmental disability
159:. Terminal deletions of
22:9q34.3 deletion syndrome
890:10.1136/jmg.2008.062950
576:10.1136/jmg.2004.028464
1122:Rare genetic syndromes
221:Respiratory infections
153:9q34 deletion syndrome
126:Smith-Magenis syndrome
117:Differential diagnosis
801:Kleefstrasyndrome.org
650:10.1038/ejhg.2012.267
558:Kleefstra, T (2005).
130:Pitt-Hopkins syndrome
616:"Kleefstra Syndrome"
526:"Kleefstra Syndrome"
490:"Kleefstra Syndrome"
375:mitral regurgitation
241:Behavioural symptoms
687:Bioscience Horizons
620:Mommies of Miracles
530:Seattle:GeneReviews
218:Childhood hypotonia
1084:Kleefstra Syndrome
1062:Kleefstra Syndrome
1048:External resources
782:2013-04-04 at the
501:Kleefstra Syndrome
495:2013-07-04 at the
199:Signs and symptoms
30:Kleefstra syndrome
1104:
1103:
614:Andrea Belanger,
453:10.1159/000335648
406:Angelman syndrome
255:Biting or hitting
233:Happy disposition
204:Physical symptoms
150:
149:
146:Tjitske Kleefstra
134:Angelman syndrome
92:Diagnostic method
16:Medical condition
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55:Medical genetics
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884:(9): 598–606.
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840:10.1086/505693
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346:Epidemiology
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300:pathogenesis
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181:microcephaly
152:
151:
1057:GeneReviews
252:Aggression
249:Sociability
246:Passiveness
224:Motor delay
142:Named after
111:sequencing.
27:Other names
1111:Categories
1022:DiseasesDB
806:3 February
543:3 February
418:References
386:intragenic
193:frameshift
173:hypoplasia
155:is a rare
76:hypoplasia
1038:724207001
1033:SNOMED CT
584:1468-6244
338:Treatment
310:Diagnosis
296:mosaicism
288:mosaicism
260:Moodiness
165:hypotonia
86:Genetics.
50:Specialty
1090:Orphanet
908:19372089
858:16826528
780:Archived
750:16931583
668:23232695
602:15805155
538:20945554
493:Archived
471:22670141
393:See also
364:Research
322:(MLPA),
318:(FISH),
268:Genetics
177:epilepsy
70:Symptoms
1016:C563043
964:LD2F.1Y
899:3395372
849:1559478
741:1867615
659:3722677
593:1736026
462:3366700
355:History
275:de novo
1095:261494
1005:610253
994:758.39
930:
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906:
896:
856:
846:
786:, 2013
766:, 2008
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622:, 2011
600:
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582:
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503:, 2009
469:
459:
410:
404:
398:
292:intron
107:, and
83:Causes
57:
1027:32302
979:Q93.5
775:N/A,
400:EHMT1
185:EHMT1
109:EHMT1
1079:GARD
1068:NORD
1011:MeSH
1000:OMIM
989:9-CM
904:PMID
854:PMID
808:2017
746:PMID
664:PMID
598:PMID
580:ISSN
545:2017
534:PMID
467:PMID
985:ICD
970:ICD
955:ICD
894:PMC
886:doi
844:PMC
836:doi
736:PMC
728:doi
695:doi
654:PMC
646:doi
588:PMC
572:doi
457:PMC
449:doi
282:.
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508:^
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426:^
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103:,
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987:-
972:-
957:-
947:D
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451::
445:2
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