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Official Journal of the European Paediatric Neurology Society
Case study
Autosomal recessive primary microcephalies (MCPH) Angela M. Kaindl a,b,* a b
Department of Pediatric Neurology, Charite´ e Universita¨tsmedizin Berlin, Germany Institute of Cell Biology and Neurobiology, Charite´ e Universita¨tsmedizin Berlin, Germany
article info
abstract
Article history:
Autosomal recessive primary microcephaly (MCPH) is a genetically heterogeneous disease
Received 23 March 2014
characterized by a pronounced reduction in volume of otherwise architectonical normal
Accepted 28 March 2014
brains and intellectual deficit. Here, we summarize the genetic causes of MCPH types 1e12 known to date. ª 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights
Keywords:
reserved.
MCPH Microcephaly Intellectual disability MCPH1 WDR62 CDK5RAP2 CASC5 ASPM CENPJ STIL CEP135 CEP152 ZNF335 PHC1 CDK6
Gene table: autosomal recessive primary microcephaly (MCPH) type 1e12. Diseasea MCPH1 MCPH2
MIM
Gene location
#251200 #604317
8p23.1 19q13.12
Gene symbol MCPH1 WDR62
MIM *607117 *613583
Protein Microcephalin WD-repeat-containing protein 62
Key references 1,2 3,4 (continued on next page)
* Department of Pediatric Neurology and Institute of Cell Biology and Neurobiology, Charite´ e Universita¨tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Tel.: þ49 30 450 566112; fax: þ49 30 450 566920. E-mail address:
[email protected]. http://dx.doi.org/10.1016/j.ejpn.2014.03.010 1090-3798/ª 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Kaindl AM, Autosomal recessive primary microcephalies (MCPH), European Journal of Paediatric Neurology (2014), http://dx.doi.org/10.1016/j.ejpn.2014.03.010
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e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 4 ) 1 e2
(continued ) Diseasea
Gene symbol
MIM
MCPH3
#604804
9q33.2
CDK5RAP2
*608201
MCPH4 MCPH5
#604321 #608716
15q15.1 1q31.3
CASC5 ASPM
*609173 *605481
MCPH6 MCPH7 MCPH8 MCPH9 MCPH10 MCPH11 MCPH12b
#608393 #612703 #614673 #614852 #615095 #615414 e
13q12.2 1p33 4q12 15q21.1 20q13.12 12p13.31 7q21.2
CENPJ STIL CEP135 CEP152 ZNF335 PHC1 CDK6
*609279 *181590 *611423 *613529 *610827 *602978 *603368
a b
MIM
Gene location
Protein Cyclin-dependent kinase 5 regulatory subunit-associated protein 2 Cancer susceptibility candidate 5 Abnormal spindle-like, microcephaly associated protein Centromeric protein J SCL/TAL1-interrupting locus protein Centrosomal protein 135 kD Centrosomal protein 152 kD Zinc finger protein 335 Polyhomeotic-like 1 protein Cyclin-dependent kinase 6
Key references 5,6 7,8 9e11 6,12 13,14 15 16 17 18 19
Mode of inheritance is autosomal recessive in all diseases listed. MCPH12 is not listed in OMIM so far.
references
1. Jackson AP, Eastwood H, Bell SM, et al. Identification of microcephalin, a protein implicated in determining the size of the human brain. Am J Hum Genet 2002;71:136e42. 2. Jackson AP, McHale DP, Campbell DA, et al. Primary autosomal recessive microcephaly (MCPH1) maps to chromosome 8p22-pter. Am J Hum Genet 1998;63:541e6. 3. Roberts E, Jackson AP, Carradice AC, et al. The second locus for autosomal recessive primary microcephaly (MCPH2) maps to chromosome 19q13.1-13.2. Eur J Hum Genet 1999;7:815e20. 4. Nicholas AK, Khurshid M, Desir J, et al. WDR62 is associated with the spindle pole and is mutated in human microcephaly. Nat Genet 2010;42:1010e4. 5. Moynihan L, Jackson AP, Roberts E, et al. A third novel locus for primary autosomal recessive microcephaly maps to chromosome 9q34. Am J Hum Genet 2000;66:724e7. 6. Bond J, Roberts E, Springell K, et al. A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. Nat Genet 2005;37:353e5. 7. Jamieson CR, Govaerts C, Abramowicz MJ. Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. Am J Hum Genet 1999;65:1465e9. 8. Genin A, Desir J, Lambert N, et al. Kinetochore KMN network gene CASC5 mutated in primary microcephaly. Hum Mol Genet 2012;21:5306e17. 9. Jamieson CR, Fryns JP, Jacobs J, et al. Primary autosomal recessive microcephaly: MCPH5 maps to 1q25-q32. Am J Hum Genet 2000;67:1575e7.
10. Pattison L, Crow YJ, Deeble VJ, et al. A fifth locus for primary autosomal recessive microcephaly maps to chromosome 1q31. Am J Hum Genet 2000;67:1578e80. 11. Bond J, Roberts E, Mochida GH, et al. ASPM is a major determinant of cerebral cortical size. Nat Genet 2002;32:316e20. 12. Leal GF, Roberts E, Silva EO, et al. A novel locus for autosomal recessive primary microcephaly (MCPH6) maps to 13q12.2. J Med Genet 2003;40:540e2. 13. Kumar A, Girimaji SC, Duvvari MR, Blanton SH. Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly. Am J Hum Genet 2009;84:286e90. 14. Darvish H, Esmaeeli-Nieh S, Monajemi GB, et al. A clinical and molecular genetic study of 112 Iranian families with primary microcephaly. J Med Genet 2010;47:823e8. 15. Hussain MS, Baig SM, Neumann S, et al. A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function. Am J Hum Genet 2012;90:871e8. 16. Guernsey DL, Jiang H, Hussin J, et al. Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4. Am J Hum Genet 2010;87:40e51. 17. Yang YJ, Baltus AE, Mathew RS, et al. Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation. Cell. 2012;151:1097e112. 18. Awad S, Al-Dosari MS, Al-Yacoub N, et al. Mutation in PHC1 implicates chromatin remodeling in primary microcephaly pathogenesis. Hum Mol Genet 2013;22:2200e13. 19. Hussain MS, Baig SM, Neumann S, et al. CDK6 associates with the centrosome during mitosis and is mutated in a large Pakistani family with primary microcephaly. Hum Mol Genet 2013;22:5199e214.
Please cite this article in press as: Kaindl AM, Autosomal recessive primary microcephalies (MCPH), European Journal of Paediatric Neurology (2014), http://dx.doi.org/10.1016/j.ejpn.2014.03.010