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表現型(遺伝子の作用と環境によって表面に出る性質)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/14 06:35:22」(JST)

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McLeod syndrome (or McLeod phenomenon; /məˈklaʊd/) is an X-linked recessive genetic disorder that may affect the blood, brain, peripheral nerves, muscle, and heart. It is caused by a variety of recessively-inherited mutations in the XK gene on the X chromosome. The gene is responsible for producing the Kx protein, a secondary supportive protein for the Kell antigen on the red blood cell surface.

Clinical features

Patients usually begin to notice symptoms in their 50s and the course is usually slowly progressive. Common features include peripheral neuropathy, cardiomyopathy, and hemolytic anemia. Other features include limb chorea, facial tics, other oral movements (lip and tongue biting), seizures, a late-onset dementia, and behavioral changes.

Laboratory features

McLeod syndrome is one of only a few disorders in which acanthocytes may be found on the peripheral blood smear. Blood evaluation may show signs of hemolytic anemia. Elevated creatine kinase can be seen with myopathy in McLeod syndrome.

Radiologic and pathologic features

MRI shows increased T2 signal in the lateral putamen with caudate atrophy and secondary lateral ventricular dilation. Necropsy shows loss of neurons and gliosis in the caudate and globus pallidus. Similar changes may also be seen in the thalamus, substantia nigra, and putamen. The cerebellum and cerebral cortex are generally spared.

History

McLeod syndrome was discovered in 1961 and, as with the Kell antigen system, was named after the first patient in which it was found: a Harvard dental student Hugh McLeod, whose red blood cells were observed to have weak expression of Kell system antigens during blood donation, and his red cells were found to be acanthocytic (spiky) under the microscope.^[1]

Genetics

The McLeod phenotype is a recessive mutation of the Kell blood group system. The McLeod gene encodes the XK protein, which is located on the X chromosome,^[2] and has the structural characteristics of a membrane transport protein but an unknown function. Absence of the XK protein is an X-linked disease. ^[3] Mutational variants result in McLeod syndrome either with or without neuroacanthocytosis: the gene on the X chromosome for McLeod syndrome is physically close to the gene for chronic granulomatous disease. As a result, an individual with one relatively small deletion may have both diseases. ^[4]

The phenotype may be present without the syndrome presenting.^[5]

Epidemiology and disease associations

McLeod syndrome is present in 0.5 to 1 per 100,000 of the population. McLeod males have variable acanthocytosis due to a defect in the inner leaflet bilayer of the red blood cell, as well as mild hemolysis. McLeod females have only occasional acanthocytes and very mild hemolysis; the lesser severity is thought to be due to X chromosome inactivation via the Lyon effect. Some individuals with McLeod phenotype develop myopathy, neuropathy, or psychiatric symptoms, producing a syndrome that may mimic chorea.^[6]^[7]

McLeod syndrome can cause an increase in the enzymes creatine kinase (CK) and lactate dehydrogenase (LDH) found in routine blood screening.^[8]

Treatment

There is no cure for McLeod syndrome; the treatment is supportive depending on symptoms. Medication may assist management of epilepsy, and cardiac and psychiatric features, although patients may respond poorly to treatment for chorea.

Prognosis

A typical patient with severe McLeod syndrome that begins in adult life lives for an additional 5 to 10 years. Patients with cardiomyopathy have elevated risk for congestive heart failure and sudden cardiac death. The prognosis for a normal life span is often good in some patients with mild neurological or cardiac sequelae.^[9]

References

^ Allen FH, Krabbe SM, Corcoran PA (September 1961). "A new phenotype (McLeod) in the Kell blood-group system". Vox Sang. 6: 555–60. doi:10.1111/j.1423-0410.1961.tb03203.x. PMID 13860532.
^ Arnaud L, Salachas F, Lucien N, et al. (March 2009). "Identification and characterization of a novel XK splice site mutation in a patient with McLeod syndrome". Transfusion 49 (3): 479–84. doi:10.1111/j.1537-2995.2008.02003.x. PMID 19040496.
^ Ho MF, Monaco AP, Blonden LA, et al. (February 1992). "Fine mapping of the McLeod locus (XK) to a 150-380-kb region in Xp21". Am. J. Hum. Genet. 50 (2): 317–30. PMC 1682457. PMID 1734714.
^ Marsh WL, Oyen R, Nichols ME, Allen FH (February 1975). "Chronic granulomatous disease and the Kell blood groups". Br. J. Haematol. 29 (2): 247–62. doi:10.1111/j.1365-2141.1975.tb01819.x. PMID 1191546.
^ Walker RH, Danek A, Uttner I, Offner R, Reid M, Lee S (February 2007). "McLeod phenotype without the McLeod syndrome". Transfusion 47 (2): 299–305. doi:10.1111/j.1537-2995.2007.01106.x. PMID 17302777.
^ Danek A, Rubio JP, Rampoldi L, et al. (December 2001). "McLeod neuroacanthocytosis: genotype and phenotype". Ann. Neurol. 50 (6): 755–64. doi:10.1002/ana.10035. PMID 11761473.
^ Malandrini A, Fabrizi GM, Truschi F, et al. (June 1994). "Atypical McLeod syndrome manifested as X-linked chorea-acanthocytosis, neuromyopathy, and dilated cardiomyopathy: report of a family". J. Neurol. Sci. 124 (1): 89–94. doi:10.1016/0022-510X(94)90016-7. PMID 7931427.
^ Oechsner M, G. Winkler G, A. Danek A, "McLeod neuroacanthocytosis: An underdiagnosed syndrome?" International communication forum in human molecular genetics September 6, 1995
^ Hewer, E; Danek, A; Schoser, B. G.; Miranda, M; Reichard, R; Castiglioni, C; Oechsner, M; Goebel, H. H.; Heppner, F. L.; Jung, H. H. (2007). "Mc Leod myopathy revisited: More neurogenic and less benign". Brain 130 (Pt 12): 3285–96. doi:10.1093/brain/awm269. PMID 18055495.

External links

GeneReview/NIH/UW entry on McLeod Neuroacanthocytosis Syndrome

UpToDate Contents

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1. 神経有棘赤血球症 neuroacanthocytosis
2. 先天性肺葉性肺気腫 congenital lobar emphysema
3. 舞踏病の概要 overview of chorea
4. 棘状細胞（棘状赤血球および有棘赤血球）と標的細胞の原因 causes of spiculated cells echinocytes and acanthocytes and target cells
5. 赤血球抗原および抗体のプライマー a primer of red blood cell antigens and antibodies

English Journal

Genetic heterogeneity beyond CYP2C8*3 does not explain differential sensitivity to paclitaxel-induced neuropathy.

Hertz DL1, Roy S, Jack J, Motsinger-Reif AA, Drobish A, Clark LS, Carey LA, Dees EC, McLeod HL.
Breast cancer research and treatment.Breast Cancer Res Treat.2014 May;145(1):245-54. doi: 10.1007/s10549-014-2910-1. Epub 2014 Apr 6.
The development of paclitaxel-induced peripheral neuropathy (PIPN) is influenced by drug exposure and patient genetics. The purpose of this analysis was to expand on a previous reported association of CYP2C8*3 and PIPN risk by investigating additional polymorphisms in CYP2C8 and in hundreds of other
PMID 24706167

Novel single base-pair deletion in exon 1 of XK gene leading to McLeod syndrome with chorea, muscle wasting, peripheral neuropathy, acanthocytosis and haemolysis.

Wiethoff S1, Xiromerisiou G2, Bettencourt C3, Kioumi A4, Tsiptsios I2, Tychalas A2, Evaggelia M2, George K4, Makris V5, Hardy J1, Houlden H1.
Journal of the neurological sciences.J Neurol Sci.2014 Apr 15;339(1-2):220-2. doi: 10.1016/j.jns.2014.01.034. Epub 2014 Feb 1.
We present a 70-year-old male patient of Greek origin with choreatic movements of the tongue and face, lower limb muscle weakness, peripheral neuropathy, elevated creatinephosphokinase (CPK), acanthocytosis and haemolysis in the absence of Kell RBC antigens with an additional Factor IX-deficiency. G
PMID 24529944

Genetic markers of toxicity from capecitabine and other fluorouracil-based regimens: investigation in the QUASAR2 study, systematic review, and meta-analysis.

Rosmarin D1, Palles C, Church D, Domingo E, Jones A, Johnstone E, Wang H, Love S, Julier P, Scudder C, Nicholson G, Gonzalez-Neira A, Martin M, Sargent D, Green E, McLeod H, Zanger UM, Schwab M, Braun M, Seymour M, Thompson L, Lacas B, Boige V, Ribelles N, Afzal S, Enghusen H, Jensen SA, Etienne-Grimaldi MC, Milano G, Wadelius M, Glimelius B, Garmo H, Gusella M, Lecomte T, Laurent-Puig P, Martinez-Balibrea E, Sharma R, Garcia-Foncillas J, Kleibl Z, Morel A, Pignon JP, Midgley R, Kerr D, Tomlinson I.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.J Clin Oncol.2014 Apr 1;32(10):1031-9. doi: 10.1200/JCO.2013.51.1857. Epub 2014 Mar 3.
PURPOSE: Fluourouracil (FU) is a mainstay of chemotherapy, although toxicities are common. Genetic biomarkers have been used to predict these adverse events, but their utility is uncertain.PATIENTS AND METHODS: We tested candidate polymorphisms identified from a systematic literature search for asso
PMID 24590654

Japanese Journal

多発性蜂窩織炎, 敗血症, 急性腎不全, 容血性貧血を合併したMcLeod表現血液型の1例

古屋志野,北澤邦彦,出浦弦,土信田文隆,清水慎介,下條隆,酒井寿明,石黒淳,宮原隆成,三澤卓夫,野口修
日本内科学会雑誌 92(1), 140-142, 2003-01-10
… 8歳,男性.腰痛・右膝痛を主訴に受診し,頸部及び右上下肢の広範な蜂窩織炎を認めた.黄色ブドウ球菌敗血症と急性腎不全を伴っており,赤血球形態異常のない溶血性貧血を合併していた.患者血液型は赤血球膜にKx抗原を欠くMcLeod型であった.血液浄化療法やステロイドパルス療法を行ったが,心不全で死亡した.本症例は多彩な合併症を呈したMcLeod表現血液型の1例であり,若干の文献的考察を加え報告した. …
NAID 10010185856

Haematological changes associated with the McLeod phenotype of the Kell blood group system

WIMER BM.
Br J Haematol 36, 219-224, 1977
NAID 30035616974

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リンク元	「マックレオド表現型」

「マックレオド表現型」

McLeod syndrome
Classification and external resources
OMIM	314850
DiseasesDB	29708
GeneReviews	McLeod Neuroacanthocytosis Syndrome;
	[edit on Wikidata]

　　[★]

英: McLeod phenotype
関: ケル抗原

[1] Allen FH, Krabbe SM, Corcoran PA (September 1961). "A new phenotype (McLeod) in the Kell blood-group system". Vox Sang. 6: 555–60. doi:10.1111/j.1423-0410.1961.tb03203.x. PMID 13860532.

[pmid19040496-2] Arnaud L, Salachas F, Lucien N, et al. (March 2009). "Identification and characterization of a novel XK splice site mutation in a patient with McLeod syndrome". Transfusion 49 (3): 479–84. doi:10.1111/j.1537-2995.2008.02003.x. PMID 19040496.

[3] Ho MF, Monaco AP, Blonden LA, et al. (February 1992). "Fine mapping of the McLeod locus (XK) to a 150-380-kb region in Xp21". Am. J. Hum. Genet. 50 (2): 317–30. PMC 1682457. PMID 1734714.

[4] Marsh WL, Oyen R, Nichols ME, Allen FH (February 1975). "Chronic granulomatous disease and the Kell blood groups". Br. J. Haematol. 29 (2): 247–62. doi:10.1111/j.1365-2141.1975.tb01819.x. PMID 1191546.

[pmid17302777-5] Walker RH, Danek A, Uttner I, Offner R, Reid M, Lee S (February 2007). "McLeod phenotype without the McLeod syndrome". Transfusion 47 (2): 299–305. doi:10.1111/j.1537-2995.2007.01106.x. PMID 17302777.

[6] Danek A, Rubio JP, Rampoldi L, et al. (December 2001). "McLeod neuroacanthocytosis: genotype and phenotype". Ann. Neurol. 50 (6): 755–64. doi:10.1002/ana.10035. PMID 11761473.

[7] Malandrini A, Fabrizi GM, Truschi F, et al. (June 1994). "Atypical McLeod syndrome manifested as X-linked chorea-acanthocytosis, neuromyopathy, and dilated cardiomyopathy: report of a family". J. Neurol. Sci. 124 (1): 89–94. doi:10.1016/0022-510X(94)90016-7. PMID 7931427.

[8] Oechsner M, G. Winkler G, A. Danek A, "McLeod neuroacanthocytosis: An underdiagnosed syndrome?" International communication forum in human molecular genetics September 6, 1995

[9] Hewer, E; Danek, A; Schoser, B. G.; Miranda, M; Reichard, R; Castiglioni, C; Oechsner, M; Goebel, H. H.; Heppner, F. L.; Jung, H. H. (2007). "Mc Leod myopathy revisited: More neurogenic and less benign". Brain 130 (Pt 12): 3285–96. doi:10.1093/brain/awm269. PMID 18055495.

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McLeod phenotype