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and Çanakkale families) it was the VLDLR gene on chromosome 9p24. This is the only family so far to express homozygosity. It is possible for dissimilar mutations in the VLDLR gene to result in the same phenotype as a result of allelic heterogeneity. In the
Iskenderun family, a different gene, WDR81 on chromosome 17p13.1–13.3 was isolated . The Iraqi family had CA8 on chromosome 8q isolated. In the last family studied (the Adana family), the researchers were not able to isolate any gene, only a locus on chromosome 13q. This isolation led to the implication of more genes as the causes of quadrupedalism. The fact that chromosome 9p24 had no effect on some families points to the genetic heterogeneity of the syndrome.
167:
150:
mutations. The researchers proposed a tentative reclassification of UTS into three types based on how they present themselves clinically. They attribute the first type (referred to as developmental UTS) to mutations in TUBB2B and VLDLR. Type II (degenerative UTS) is linked to ATP8A2 and WDR81 while type III (UTS without cerebral malformations) implicates CA8.
149:
Researchers recently isolated a recessive TUBB2B mutation in one of the families diagnosed with UTS. This makes TUBB2B the fifth gene after VLDLR, WDR81, CA8 and ATP8A2, associated with this syndrome. Patients with mutations of TUBB2B are phenotypically similar to those with VLDLR, WDR81 and ATP8A2
145:
Another approach for establishing the genealogy has been to compare UTS with similar syndromes such as disequilibrium syndrome (DES) and
Joubert syndrome. UTS seems to be genetically different from DES in that DES can be linked to a single gene, VLDLR, located on chromosome 9p24. When compared with
141:
The researchers took a different approach to isolate the gene that causes this syndrome by comparing the genealogy of all the families in which the syndrome had been reported. The two types of Uner Tan
Syndrome, UTS type I and type II show genetic heterogeneity. In two of the first families (Antep
78:
has been the primary example of the proposed syndrome. Tan described five members as walking with a quadrupedal gait using their feet and the palms of their hands. In infants, where this is a rare stage prior and sometimes following bipedal walking, such a gait is called "bear crawl". The affected
153:
The problem with identifying the specific mutation that leads to Uner Tan syndrome is the fact that different mutations in a single gene can lead to a wide range of phenotypes. In the VLDLR gene, similar mutations may be responsible for different types of cerebellar ataxias that affect proper
133:
within the brain. Ozcelik found mutations in the VLDLR gene in affected individuals, and suggested that these specific mutations may lead to VLDLR deficiency during the development of the brain. This may affect the proper formation of cerebrocerebellar structures critical for upright walking,
243:
It's terribly easy to be led away by some notion of living fossils... I'm not going to make any bones about this. I think that
Professor Tan's description of this family as a "devolution", as an evolutionary throwback, is not only scientifically irresponsible, but is deeply insulting to this
215:
have argued that the gait of these individuals is due to two rare phenomena coming together, not atavism. First, instead of initially crawling as infants on their knees, they started off learning to move around with a "bear crawl" on their feet. Second, due to their
106:. This simply means it is a type of disorder that involves the cerebellum becoming inflamed, resulting in lack of control of voluntary movements. Uner Tan syndrome falls into this category because it has similar symptoms to other cerebellar ataxia disorders such as
134:
resulting in quadrupedal locomotion. Other genes may also be involved in habitual quadrupedalism. For example, in some affected families, chromosome 17p13 was involved, while in other families 17p13 and 9p24 had no effect. This suggests the syndrome is genetically
634:
Breuss, Martin W.; Nguyen, Thai; Srivatsan, Anjana; Leca, Ines; Tian, Guoling; Fritz, Tanja; Hansen, Andi H.; Musaev, Damir; McEvoy-Venneri, Jennifer; James, Kiely N.; Rosti, Rasim O.; Scott, Eric; Tan, Uner; Kolodner, Richard D.; Cowan, Nicholas J.;
102:. The syndrome's main characteristic is habitual quadrupedalism, meaning they can stand up straight until they try to move, then they walk on their hands and knees. According to Tan, the syndrome may be placed in its own category under types of
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Four other unrelated cases in families are described as having various degrees of UTS. Two males are unable to stand up, while in other cases, can stand up but cannot make a step when standing. Less severe cases use
146:
DES, Joubert syndrome has shown links to seven gene mutations. As is the case with almost all diseases, the three syndromes compared show allelic heterogeneity.
511:"Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion"
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236:
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Schmahmann JD (August 2004). "Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome".
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family members also have learning disabilities and their speech is affected. Tan proposed that these are symptoms of Uner Tan syndrome.
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58:
417:"Mutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans"
125:
Human geneticist Tayfun
Ozcelik discovered homozygosity in a region on chromosome 9p24 in Uner Tan syndrome individuals. The
305:"A new syndrome with quadrupedal gait, primitive speech, and severe mental retardation as a live model for human evolution"
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Onat OE, Gulsuner S, Bilguvar K, Nazli Basak A, Topaloglu H, Tan M, Tan U, Gunel M, Ozcelik T (March 2013).
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Uner Tan syndrome has been linked to intrafamilial marriage and reproduction, which suggests that it is an
34:
82:
In
January 2008, Tan reported on another family (four males and two females) located in southern Turkey.
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Enhancing
Cognitive Performances of Individuals with Intellectual Disabilities: A Human Factors Approach
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726:"Uner tan syndrome: history, clinical evaluations, genetics, and the dynamics of human quadrupedalism"
585:"Uner tan syndrome: history, clinical evaluations, genetics, and the dynamics of human quadrupedalism"
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641:"Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability"
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Ozcelik T, Akarsu N, Uz E, Caglayan S, Gulsuner S, Onat OE, Tan M, Tan U (March 2008).
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Medical condition characterized by abnormal gait and severe learning difficulties
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Proceedings of the
National Academy of Sciences of the United States of America
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gene (VLDLR) is located in this region, which is involved in the migration of
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Tan U, Karaca S, Tan M, Yilmaz B, Bagci NK, Ozkur A, Pence S (January 2008).
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706:. London, UK: Centre for Philosophy of Natural and Social Science.
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was channeled into turning their bear crawl into a substitute for
780:"Human Quadrupeds, Primate Quadrupedalism, and Uner Tan Syndrome"
360:"Unertan syndrome: a case series demonstrating human devolution"
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52:" (atavism). The proposed syndrome was featured in the 2006
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The
Journal of Neuropsychiatry and Clinical Neurosciences
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90:, which is a normal phase in child gait development.
235:Üner Tan and colleagues claim that UTS differs from
110:(DES-H) and Cayman Syndrome. These symptoms include
697:"Hand-walkers: five siblings who never stood up"
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224:on two legs difficult. Because of this, their
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48:. Tan postulated that this is an example of "
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695:Humphrey N, Keynes R, Skoyles JR (2005).
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367:The International Journal of Neuroscience
312:The International Journal of Neuroscience
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558:Carlin, Michael T. (15 February 2012).
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277:VLDLR-associated cerebellar hypoplasia
127:very low density lipoprotein receptor
40:. People affected by UTS walk with a
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273:, documentary about the Ulas family
515:European Journal of Human Genetics
270:The Family That Walks On All Fours
255:The Family That Walks on All Fours
59:The Family That Walks On All Fours
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44:locomotion and often have severe
562:. INTECH Open Access Publisher.
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74:of nineteen from rural southern
778:Shapiro, Liza J (2014-07-16).
122:of the cerebellum and vermis.
1:
639:; Gleeson, Joseph G. (2016).
220:brain impairment, they found
797:10.1371/journal.pone.0101758
100:autosomal recessive disorder
743:10.2174/1874205X01004010078
602:10.2174/1874205X01004010078
30:that was discovered by the
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730:The Open Neurology Journal
589:The Open Neurology Journal
379:10.1080/00207450701667857
324:10.1080/00207450500455330
202:evolutionary psychologist
645:Human Molecular Genetics
369:(Submitted manuscript).
583:Tan, U (16 July 2010).
442:10.1073/pnas.0710010105
237:disequilibrium syndrome
108:disequilibrium syndrome
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211:and medical scientist
154:locomotion in humans.
35:evolutionary biologist
527:10.1038/ejhg.2012.170
46:learning disabilities
488:10.1176/jnp.16.3.367
303:Tan U (March 2006).
724:Tan U (July 2010).
433:2008PNAS..105.4232O
840:Gait abnormalities
657:10.1093/hmg/ddw383
177:. You can help by
104:cerebellar ataxias
569:978-953-307-865-6
250:Nicholas Humphrey
226:motor development
209:Nicholas Humphrey
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50:reverse evolution
20:Uner Tan syndrome
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186:February 2022
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173:This section
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318:(3): 361–9.
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213:John Skoyles
205:Roger Keynes
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179:adding to it
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56:documentary
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373:(1): 1–25.
131:neuroblasts
88:toe walking
72:Ulaş family
42:quadrupedal
829:Categories
283:References
230:bipedalism
218:congenital
120:hypoplasia
112:dysarthria
835:Syndromes
736:: 78–89.
595:: 78–89.
222:balancing
158:Criticism
116:nystagmus
816:25029457
784:PLOS ONE
762:21258577
675:28013290
621:21258577
545:22892528
496:15377747
461:18326629
395:14557995
387:18041603
332:16484061
263:See also
247:—
94:Genetics
38:Üner Tan
28:syndrome
807:4100729
753:3024602
666:6075555
612:3024602
536:3573203
452:2393756
429:Bibcode
340:6482447
244:family.
66:History
32:Turkish
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363:(PDF)
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308:(PDF)
26:is a
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758:PMID
671:PMID
617:PMID
564:ISBN
541:PMID
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457:PMID
383:PMID
328:PMID
200:and
70:The
54:BBC2
24:UTS)
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792:doi
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738:doi
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