Phenotypes and genotypes in non-consanguineous and consanguineous primary microcephaly: High incidence of epilepsy

brain developmental disorders; consanguinity; epilepsy; Mendeliome; primary microcephaly; rare disease; ASPM protein, human; cell cycle protein; nerve protein; WDR62 protein, human; child; complication; female; gene frequency; genetic heterogeneity; genetics; genotype; human; incidence; male; microcephaly; pathology; phenotype; Cell Cycle Proteins; Child; Consanguinity; Epilepsy; Female; Gene Frequency; Genetic Heterogeneity; Genotype; Humans; Incidence; Male; Microcephaly; Nerve Tissue Proteins; Phenotype

Abstract :

[en] Background: Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. Methods: We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Results: Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non-consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Conclusion: Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients. © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC

Disciplines :

Genetics & genetic processes

Author, co-author :

Duerinckx, S.; Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire, Université Libre de Bruxelles, Brussels, Belgium

Désir, J.; Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, Belgium

Perazzolo, C.; Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire, Université Libre de Bruxelles, Brussels, Belgium

Badoer, C.; Department of Genetics, Hôpital Erasme, ULB Center of Human Genetics, Université Libre de Bruxelles, Brussels, Belgium

Jacquemin, V.; Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire, Université Libre de Bruxelles, Brussels, Belgium

Soblet, J.; Department of Genetics, Hôpital Erasme, ULB Center of Human Genetics, Université Libre de Bruxelles, Brussels, Belgium, Hôpital Universitaire des Enfants Reine Fabiola (HUDERF), Université Libre de Bruxelles, Brussels, Belgium

Maystadt, I.; Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, Belgium

Tunca, Y.; Department of Medical Genetics, Gülhane Faculty of Medicine & Gülhane Training and Research Hospital, University of Health Sciences Turkey, Ankara, Turkey

Blaumeiser, B.; University and University Hospital of Antwerp, Antwerp, Belgium

Ceulemans, B.; University and University Hospital of Antwerp, Antwerp, Belgium

More authors (28 more)

Language :

English

Title :

Phenotypes and genotypes in non-consanguineous and consanguineous primary microcephaly: High incidence of epilepsy

Publication date :

2021

Journal title :

Molecular Genetics and Genomic Medicine

eISSN :

2324-9269

Publisher :

John Wiley and Sons Inc

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Funding text :

This work was supported by ERA‐net E‐Rare Euromicro and the Action de Recherche Concertée (ARC) of the Belgian Fédération Wallonie Bruxelles to M.A., the Fonds de la Recherche Scientifique FRS‐FNRS Belgium and the Fonds de soutien Marguerite‐Marie Delacroix to S.D., the Fonds Erasme to M.A. and to S.D., and the Université Libre de Bruxelles to I.P.

Available on ORBi :

since 26 January 2024

Statistics

Number of views

13 (0 by ULiège)

Number of downloads

5 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Arai, E., Gotoh, M., Tian, Y., Sakamoto, H., Ono, M., Matsuda, A., Takahashi, Y., Miyata, S., Totsuka, H., Chiku, S., Komiyama, M., & Fujimoto, H. (2015). Alterations of the spindle checkpoint pathway in clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas. International Journal of Cancer, 137, 2589–2606.
Armakolas, A., & Klar, A. J. S. (2007). Left-right dynein motor implicated in selective chromatid segregation in mouse cells. Science, 315, 100–101. https://doi.org/10.1126/science.1129429
Bhat, V., Girimaji, S. C., Mohan, G., Arvinda, H. R., Singhmar, P., Duvvari, M. R., & Kumar, A. (2011). Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations. Clinical Genetics, 80, 532–540. https://doi.org/10.1111/j.1399-0004.2011.01686.x
Boonsawat, P., Joset, P., Steindl, K., Oneda, B., Gogoll, L., Azzarello-Burri, S., Sheth, F., Datar, C., Verma, I. C., Puri, R. D., Zollino, M., Bachmann-Gagescu, R., Niedrist, D., Papik, M., Figueiro-Silva, J., Masood, R., Zweier, M., Kraemer, D., Lincoln, S., … Rauch, A. (2019). Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly. Genetics in Medicine, 21(9), 2043–2058. https://doi.org/10.1038/s41436-019-0464-7
Bond, J., Scott, S., Hampshire, D. J., Springell, K., Corry, P., Abramowicz, M. J., Mochida, G. H., Hennekam, R. C. M., Maher, E. R., Fryns, J.-P., Alswaid, A., Jafri, H., Rashid, Y., Mubaidin, A., Walsh, C. A., Roberts, E., & Woods, C. G. (2003). Protein-truncating mutations in ASPM cause variable reduction in brain size. American Journal of Human Genetics, 73, 1170–1177.
Cavallin, M., Bery, A., Maillard, C., Salomon, L. J., Bole, C., Reilly, M. L., Nitschké, P., Boddaert, N., & Bahi-Buisson, N. (2018). Recurrent RTTN mutation leading to severe microcephaly, polymicrogyria and growth restriction. European Journal of Medical Genetics, 61, 755–758. https://doi.org/10.1016/j.ejmg.2018.08.001
Chapelin, C., Duriez, B., Magnino, F., Goossens, M., Escudier, E., & Amselem, S. (1997). Isolation of several human axonemal dynein heavy chain genes: Genomic structure of the catalytic site, phylogenetic analysis and chromosomal assignment. FEBS Letters, 412, 325–330. https://doi.org/10.1016/S0014-5793(97)00800-4
Cingolani, P., Platts, A., Wang, L. L., Coon, M., Nguyen, T., Wang, L., Land, S. J., Lu, X., & Ruden, D. M. (2012). A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly, 6, 80–92. https://doi.org/10.4161/fly.19695
Cox, J., Jackson, A. P., Bond, J., & Woods, C. G. (2006). What primary microcephaly can tell us about brain growth. Trends in Molecular Medicine, 12, 358–366. https://doi.org/10.1016/j.molmed.2006.06.006
Darvish, H., Esmaeeli-Nieh, S., Monajemi, G. B., Mohseni, M., Ghasemi-Firouzabadi, S., Abedini, S. S., Bahman, I., Jamali, P., Azimi, S., Mojahedi, F., Dehghan, A., Shafeghati, Y., Jankhah, A., Falah, M., Soltani Banavandi, M. J., Ghani-Kakhi, M., Garshasbi, M., Rakhshani, F., Naghavi, A., … Najmabadi, H. (2010). A clinical and molecular genetic study of 112 Iranian families with primary microcephaly. Journal of Medical Genetics, 47, 823–828. https://doi.org/10.1136/jmg.2009.076398
DePristo, M. A., Banks, E., Poplin, R., Garimella, K. V., Maguire, J. R., Hartl, C., Philippakis, A. A., del Angel, G., Rivas, M. A., Hanna, M., McKenna, A., Fennell, T. J., Kernytsky, A. M., Sivachenko, A. Y., Cibulskis, K., Gabriel, S. B., Altshuler, D., & Daly, M. J. (2011). A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nature Genetics, 43, 491–498. https://doi.org/10.1038/ng.806
Desir, J., Abramowicz, M., & Tunca, Y. (2006). Novel mutations in prenatal diagnosis of primary microcephaly. Prenatal Diagnosis, 26, 989.
Desir, J., Cassart, M., David, P., Van Bogaert, P., & Abramowicz, M. (2008). Primary microcephaly with ASPM mutation shows simplified cortical gyration with antero-posterior gradient pre- and post-natally. American Journal of Medical Genetics Part A, 146A, 1439–1443.
Dohrn, M. F., & Bolaños, J. P. (2019). Does APC/CCDH1 control the human brain size?: An Editorial Highlight for “A novel human Cdh1 mutation impairs anaphase-promoting complex/cyclosome (APC/C) activity resulting in microcephaly, psychomotor retardation, and epilepsy” on page 103. Journal of Neurochemistry, 151, 8–10.
Duerinckx, S., & Abramowicz, M. (2018). The genetics of congenitally small brains. Seminars in Cell & Developmental Biology, 76, 76–85. https://doi.org/10.1016/j.semcdb.2017.09.015
Duerinckx, S., Jacquemin, V., Drunat, S., Vial, Y., Passemard, S., Perazzolo, C., Massart, A., Soblet, J., Racapé, J., Desmyter, L., Badoer, C., Papadimitriou, S., Le Borgne, Y.-A., Lefort, A., Libert, F., De Maertelaer, V., Rooman, M., Costagliola, S., Verloes, A., … Abramowicz, M. (2020). Digenic inheritance of human primary microcephaly delineates centrosomal and non-centrosomal pathways. Human Mutation, 41, 512–524. https://doi.org/10.1002/humu.23948.
Duerinckx, S., Meuwissen, M., Perazzolo, C., Desmyter, L., Pirson, I., & Abramowicz, M. (2018). Phenotypes in siblings with homozygous mutations of TRAPPC9 and/or MCPH1 support a bifunctional model of MCPH1. Molecular Genetics & Genomic Medicine. 6(4):660–665.
Duerinckx, S., Verhelst, H., Perazzolo, C., David, P., Desmyter, L., Pirson, I., & Abramowicz, M. (2017). Severe congenital microcephaly with AP4M1 mutation, a case report. BMC Medical Genetics, 18, 48.
Duijkers, F. A., McDonald, A., Janssens, G. E., Lezzerini, M., Jongejan, A., van Koningsbruggen, S., Leeuwenburgh-Pronk, W. G., Wlodarski, M. W., Moutton, S., Tran-Mau-Them, F., Thauvin-Robinet, C., Faivre, L., Monaghan, K. G., Smol, T., Boute-Benejean, O., Ladda, R. L., Sell, S. L., Bruel, A.-L., Houtkooper, R. H., & MacInnes, A. W. (2019). HNRNPR variants that impair homeobox gene expression drive developmental disorders in humans. American Journal of Human Genetics, 104, 1040–1059. https://doi.org/10.1016/j.ajhg.2019.03.024
Farooq, M., Lindbæk, L., Krogh, N., Doganli, C., Keller, C., Mönnich, M., Gonçalves, A. B., Sakthivel, S., Mang, Y., Fatima, A., Andersen, V. S., Hussain, M. S., Eiberg, H., Hansen, L., Kjaer, K. W., Gopalakrishnan, J., Pedersen, L. B., Møllgård, K., Nielsen, H., … Larsen, L. A. (2020). RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis. Nature Communications, 11, 5816. https://doi.org/10.1038/s41467-020-19658-0
Gardner, J., Cushion, T., Niotakis, G., Olson, H., Grant, P., Scott, R., Stoodley, N., Cohen, J., Naidu, S., Attie-Bitach, T., Bonnières, M., Boutaud, L., Encha-Razavi, F., Palmer-Smith, S., Mugalaasi, H., Mullins, J., Pilz, D., & Fry, A. (2018). Clinical and Functional Characterization of the Recurrent TUBA1A p.(Arg2His) Mutation. Brain Sciences, 8(8), 145. https://doi.org/10.3390/brainsci8080145
Genin, A., Desir, J., Lambert, N., Biervliet, M., Van Der Aa, N., Pierquin, G., Killian, A., Tosi, M., Urbina, M., Lefort, A., Libert, F., Pirson, I., & Abramowicz, M. (2012). Kinetochore KMN network gene CASC5 mutated in primary microcephaly. Human Molecular Genetics, 21, 5306–5317. https://doi.org/10.1093/hmg/dds386
Grandone, A., Torella, A., Santoro, C., Giugliano, T., Del Vecchio, B. F., Mutarelli, M., Cirillo, M., Cirillo, G., Piluso, G., Capristo, C., Festa, A., & Marzuillo, P. (2016). Expanding the phenotype of RTTN variations: A new family with primary microcephaly, severe growth failure, brain malformations and dermatitis. Clinical Genetics, 90, 445–450.
Guernsey, D. L., Jiang, H., Hussin, J., Arnold, M., Bouyakdan, K., Perry, S., Babineau-Sturk, T., Beis, J., Dumas, N., Evans, S. C., Ferguson, M., Matsuoka, M., Macgillivray, C., Nightingale, M., Patry, L., Rideout, A. L., Thomas, A., Orr, A., Hoffmann, I., … Samuels, M. E. (2010). Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4. American Journal of Human Genetics, 87, 40–51.
Gul, A., Hassan, M. J., Mahmood, S., Chen, W., Rahmani, S., Naseer, M. I., Dellefave, L., Muhammad, N., Rafiq, M. A., Ansar, M., Chishti, M. S., Ali, G., Siddique, T., & Ahmad, W. (2006). Genetic studies of autosomal recessive primary microcephaly in 33 Pakistani families: Novel sequence variants in ASPM gene. Neurogenetics, 7, 105–110. https://doi.org/10.1007/s10048-006-0042-4
Hebebrand, M., Hüffmeier, U., Trollmann, R., Hehr, U., Uebe, S., Ekici, A. B., Kraus, C., Krumbiegel, M., Reis, A., Thiel, C. T., & Popp, B. (2019). The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy. Orphanet Journal of Rare Diseases, 14, 38. https://doi.org/10.1186/s13023-019-1020-x
Igoillo-Esteve, M., Genin, A., Lambert, N., Désir, J., Pirson, I., Abdulkarim, B., Simonis, N., Drielsma, A., Marselli, L., Marchetti, P., Vanderhaeghen, P., Eizirik, D. L., Wuyts, W., Julier, C., Chakera, A. J., Ellard, S., Hattersley, A. T., Abramowicz, M., & Cnop, M. (2013). tRNA methyltransferase homolog gene TRMT10A mutation in young onset diabetes and primary microcephaly in humans. PLoS Genetics, 9, e1003888.
Jamieson, C. R., Fryns, J. P., Jacobs, J., Matthijs, G., & Abramowicz, M. J. (2000). Primary autosomal recessive microcephaly: MCPH5 maps to 1q25-q32. American Journal of Human Genetics, 67, 1575–1577.
Jamieson, C. R., Govaerts, C., & Abramowicz, M. J. (1999). Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. American Journal of Human Genetics, 65, 1465–1469.
Karczewski, K. J., Francioli, L. C., Tiao, G., Cummings, B. B., Alföldi, J., Wang, Q., Collins, R. L., Laricchia, K. M., Ganna, A., Birnbaum, D. P., Gauthier, L. D., Brand, H., Solomonson, M., Watts, N. A., Rhodes, D., Singer-Berk, M., England, E. M., Seaby, E. G., Kosmicki, J. A., … MacArthur, D. G. (2020). The mutational constraint spectrum quantified from variation in 141,456 humans. Nature, 581, 434–443. https://doi.org/10.1038/s41586-020-2308-7
Kircher, M., Witten, D. M., Jain, P., O’Roak, B. J., Cooper, G. M., & Shendure, J. (2014). A general framework for estimating the relative pathogenicity of human genetic variants. Nature Genetics, 46, 310–315. https://doi.org/10.1038/ng.2892
Kousi, M., & Katsanis, N. (2016). The genetic basis of hydrocephalus. Annual Review of Neuroscience, 39, 409–435. https://doi.org/10.1146/annurev-neuro-070815-014023
Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., Cummings, B. B., Tukiainen, T., Birnbaum, D. P., Kosmicki, J. A., Duncan, L. E., Estrada, K., Zhao, F., Zou, J., Pierce-Hoffman, E., Berghout, J., … MacArthur, D. G. (2016). Analysis of protein-coding genetic variation in 60,706 humans. Nature, 536, 285–291. https://doi.org/10.1038/nature19057
Létard, P., Drunat, S., Vial, Y., Duerinckx, S., Ernault, A., Amram, D., Arpin, S., Bertoli, M., Busa, T., Ceulemans, B., Desir, J., & Doco-Fenzy, M. (2018). Autosomal recessive primary microcephaly due to ASPM mutations: An update. Human Mutation, 39, 319–332.
Li, H., & Durbin, R. (2009). Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinforma Oxf Engl, 25, 1768–1760. https://doi.org/10.1093/bioinformatics/btp324
Li, Y., Sha, Y., Wang, X., Ding, L., Liu, W., Ji, Z., Mei, L., Huang, X., Lin, S., Kong, S., Lu, J., & Qin, W. (2019). DNAH2 is a novel candidate gene associated with multiple morphological abnormalities of the sperm flagella. Clinical Genetics, 95, 590–600.
Liu, X., Jian, X., & Boerwinkle, E. (2011). dbNSFP: A lightweight database of human nonsynonymous snps and their functional predictions. Human Mutation, 32, 894–899. https://doi.org/10.1002/humu.21517
Mefford, H. C., Sharp, A. J., Baker, C., Itsara, A., Jiang, Z., Buysse, K., Huang, S., Maloney, V. K., Crolla, J. A., Baralle, D., Collins, A., Mercer, C., Norga, K., de Ravel, T., Devriendt, K., Bongers, E. M. H. F., de Leeuw, N., Reardon, W., Gimelli, S., … Eichler, E. E. (2008). Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. New England Journal of Medicine, 359, 1685–1699. https://doi.org/10.1056/NEJMoa0805384
Mori, H., Sakakibara, S., Imai, T., Nakamura, Y., Iijima, T., Suzuki, A., Yuasa, Y., Takeda, M., & Okano, H. (2001). Expression of mouse igf2 mRNA-binding protein 3 and its implications for the developing central nervous system. Journal of Neuroscience Research, 64, 132–143. https://doi.org/10.1002/jnr.1060
Nardello, R., Fontana, A., Antona, V., Beninati, A., Mangano, G. D., Stallone, M. C., & Mangano, S. (2018). A novel mutation of WDR62 gene associated with severe phenotype including infantile spasm, microcephaly, and intellectual disability. Brain and Development, 40, 58–64. https://doi.org/10.1016/j.braindev.2017.07.003
Nasser, H., Vera, L., Elmaleh-Bergès, M., Steindl, K., Letard, P., Teissier, N., Ernault, A., Guimiot, F., Afenjar, A., Moutard, M. L., Héron, D., & Alembik, Y. (2020). CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects. Journal of Medical Genetics, 57, 389–399.
Nicholas, A. K., Khurshid, M., Désir, J., Carvalho, O. P., Cox, J. J., Thornton, G., Kausar, R., Ansar, M., Ahmad, W., Verloes, A., Passemard, S., Misson, J.-P., Lindsay, S., Gergely, F., Dobyns, W. B., Roberts, E., Abramowicz, M., & Woods, C. G. (2010). WDR62 is associated with the spindle pole and is mutated in human microcephaly. Nature Genetics, 42, 1010–1014.
Passemard, S., Titomanlio, L., Elmaleh, M., Afenjar, A., Alessandri, J.-L., Andria, G., de Villemeur, T. B., Boespflug-Tanguy, O., Burglen, L., Del Giudice, E., Guimiot, F., Hyon, C., Isidor, B., Megarbane, A., Moog, U., Odent, S., Hernandez, K., Pouvreau, N., Scala, I., … Verloes, A. (2009). Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations. Neurology, 73, 962–969. https://doi.org/10.1212/WNL.0b013e3181b8799a
Pulvers, J. N., Journiac, N., Arai, Y., & Nardelli, J. (2015). MCPH1: A window into brain development and evolution. Front Cell Neurosci, 9, 92. https://doi.org/10.3389/fncel.2015.00092
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., & Rehm, H. L. (2015). Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17, 405–424. https://doi.org/10.1038/gim.2015.30
Roberts, E., Hampshire, D. J., Pattison, L., Springell, K., Jafri, H., Corry, P., Mannon, J., Rashid, Y., Crow, Y., Bond, J., & Woods, C. G. (2002). Autosomal recessive primary microcephaly: An analysis of locus heterogeneity and phenotypic variation. Journal of Medical Genetics, 39, 718–721. https://doi.org/10.1136/jmg.39.10.718
Rodríguez, C., Sánchez-Morán, I., Álvarez, S., Tirado, P., Fernández-Mayoralas, D. M., Calleja-Pérez, B., Almeida, Á., & Fernández-Jaén, A. (2019). A novel human Cdh1 mutation impairs anaphase promoting complex/cyclosome activity resulting in microcephaly, psychomotor retardation, and epilepsy. Journal of Neurochemistry, 151, 103–115. https://doi.org/10.1111/jnc.14828
Rollins, J. D., Collins, J. S., & Holden, K. R. (2010). United States head circumference growth reference charts: Birth to 21 years. Journal of Pediatrics, 156:907–913.
Romaniello, R., Arrigoni, F., Fry, A. E., Bassi, M. T., Rees, M. I., Borgatti, R., Pilz, D. T., & Cushion, T. D. (2018). Tubulin genes and malformations of cortical development. European Journal of Medical Genetics, 61, 744–754. https://doi.org/10.1016/j.ejmg.2018.07.012
Ruaud, L., Drunat, S., Elmaleh-Bergès, M., Ernault, A., Guilmin Crepon, S., El Ghouzzi, V., Auvin, S., Verloes, A., Passemard, S., & the MCPH consortium. Neurological and developmental outcomes in WDR62 primary microcephaly. In preparation.
Rump, P., Jazayeri, O., van Dijk-Bos, K. K., Johansson, L. F., van Essen, A. J., Verheij, J. B. G. M., Veenstra-Knol, H. E., Redeker, E. J. W., Mannens, M. M. A. M., Swertz, M. A., Alizadeh, B. Z., van Ravenswaaij-Arts, C. M. A., Sinke, R. J., & Sikkema-Raddatz, B. (2016). Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly. BMC Medical Genomics, 9, 7. https://doi.org/10.1186/s12920-016-0167-8
Saadi, A., Verny, F., Siquier-Pernet, K., Bole-Feysot, C., Nitschke, P., Munnich, A., Abada-Dendib, M., Chaouch, M., Abramowicz, M., & Colleaux, L. (2016). Refining the phenotype associated with CASC5 mutation. Neurogenetics, 17, 71–78. https://doi.org/10.1007/s10048-015-0468-7
Sajid Hussain, M., Marriam Bakhtiar, S., Farooq, M., Anjum, I., Janzen, E., Reza Toliat, M., Eiberg, H., Kjaer, K. W., Tommerup, N., Noegel, A. A., Nürnberg, P., Baig, S. M., & Hansen, L. (2013). Genetic heterogeneity in Pakistani microcephaly families. Clinical Genetics, 83, 446–451. https://doi.org/10.1111/j.1399-0004.2012.01932.x
Shaheen, R., Maddirevula, S., Ewida, N., Alsahli, S., Abdel-Salam, G. M. H., Zaki, M. S., Tala, S. A., Alhashem, A., Softah, A., Al-Owain, M., Alazami, A. M., Abadel, B., Patel, N., Al-Sheddi, T., Alomar, R., Alobeid, E., Ibrahim, N., Hashem, M., Abdulwahab, F., … Alkuraya, F. S. (2019). Genomic and phenotypic delineation of congenital microcephaly. Genetics in Medicine, 21, 545–552. https://doi.org/10.1038/s41436-018-0140-3
Shamseldin, H., Alazami, A. M., Manning, M., Hashem, A., Caluseiu, O., Tabarki, B., Esplin, E., Schelley, S., Innes, A. M., Parboosingh, J. S., Lamont, R., Majewski, J., Bernier, F. P., & Alkuraya, F. S. (2015). RTTN mutations cause primary microcephaly and primordial dwarfism in humans. The American Journal of Human Genetics, 97(6), 862–868. https://doi.org/10.1016/j.ajhg.2015.10.012
Shen, J., Eyaid, W., Mochida, G. H., Al-Moayyad, F., Bodell, A., Woods, C. G., & Walsh, C. A. (2005). ASPM mutations identified in patients with primary microcephaly and seizures. Journal of Medical Genetics, 42, 725–729. https://doi.org/10.1136/jmg.2004.027706
Shen, J., Gilmore, E. C., Marshall, C. A., Haddadin, M., Reynolds, J. J., Eyaid, W., Bodell, A., Barry, B., Gleason, D., Allen, K., Ganesh, V. S., Chang, B. S., Grix, A., Hill, R. S., Topcu, M., Caldecott, K. W., Barkovich, A. J., & Walsh, C. A. (2010). Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. Nature Genetics, 42, 245–249. https://doi.org/10.1038/ng.526
Stouffs, K., Moortgat, S., Vanderhasselt, T., Vandervore, L., Dica, A., Mathot, M., Keymolen, K., Seneca, S., Gheldof, A., De Meirleir, L., & Jansen, A. C. (2018). Biallelic mutations in RTTN are associated with microcephaly, short stature and a wide range of brain malformations. European Journal of Medical Genetics, 61, 733–737. https://doi.org/10.1016/j.ejmg.2018.06.001
Tan, C. A., del Gaudio, D., Dempsey, M. A., Arndt, K., Botes, S., Reeder, A., & Das, S. (2014). Analysis of ASPM in an ethnically diverse cohort of 400 patient samples: perspectives of the molecular diagnostic laboratory. Clinical Genetics, 85, 353–358.
Tunca, Y., Vurucu, S., Parma, J., Akin, R., Désir, J., Baser, I., Ergun, A., & Abramowicz, M. (2006). Prenatal diagnosis of primary microcephaly in two consanguineous families by confrontation of morphometry with DNA data. Prenatal Diagnosis, 26, 449–453.
Valverde, R., Edwards, L., & Regan, L. (2008). Structure and function of KH domains. FEBS Journal, 275, 2712–2726. https://doi.org/10.1111/j.1742-4658.2008.06411.x
Verloes, A., Drunat, S., Gressens, P., & Passemard, S. (1993). Primary autosomal recessive microcephalies and seckel syndrome spectrum disorders. In R. A. Pagon, M. P. Adam, H. H. Ardinger, T. D. Bird, C. R. Dolan, C.-T. Fong, R. J. Smith, & K. Stephens (Eds.), GeneReviews(®). University of Washington, Seattle.
Vertii, A., Hehnly, H., & Doxsey, S. (2016). The centrosome, a multitalented renaissance organelle. Cold Spring Harbor Perspectives in Biology, 8(12), a025049. https://doi.org/10.1101/cshperspect.a025049
Woods, C. G., & Basto, R. (2014). Microcephaly. Current Biology, 24, R1109–R1111. https://doi.org/10.1016/j.cub.2014.09.063
Zaqout, S., Morris-Rosendahl, D., & Kaindl, A. M. (2017). Autosomal recessive primary microcephaly (MCPH): An update. Neuropediatrics, 48, 135–142. https://doi.org/10.1055/s-0037-1601448
Zombor, M., Kalmár, T., Nagy, N., Berényi, M., Telcs, B., Maróti, Z., Brandau, O., & Sztriha, L. (2019). A novel WDR62 missense mutation in microcephaly with abnormal cortical architecture and review of the literature. Journal of Applied Genetics, 60, 151–162. https://doi.org/10.1007/s13353-019-00486-y