A novel de novo germline mutation Glu40Lys in AKT3 causes megalencephaly with growth hormone deficiency

American Journal of Medical Genetics, Part A

Volumn 173, Issue 4, 2017, Pages 1071-1076

  Takagi, Masaki ^a   Dobashi, Kazushige ^b   Nagahara, Keiko ^b   Kato, Mitsuhiro ^b   Nishimura, Gen ^c   Fukuzawa, Ryuji ^c   Narumi, Satoshi ^a,d   Hasegawa, Tomonobu ^a  

^a KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b SHOWA UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^c TOKYO METROPOLITAN CHILDREN'S MEDICAL CENTER   (Japan)

^d NATIONAL RESEARCH INSTITUTE FOR CHILD HEALTH AND DEVELOPMENT   (Japan)

Author keywords

AKT3; growth hormone deficiency; megalencephaly

Indexed keywords

GROWTH HORMONE; RECOMBINANT GROWTH HORMONE; AKT3 PROTEIN, HUMAN; PROTEIN KINASE B;

AKT3 GENE; ALEXANDER DISEASE; ARTICLE; CASE REPORT; CHILD; CLINICAL FEATURE; DEVELOPMENTAL GENE; DISEASE ACTIVITY; DISEASE ASSOCIATION; GENE EXPRESSION; GENE FUNCTION; GENE IDENTIFICATION; GERMLINE MUTATION; GROWTH HORMONE DEFICIENCY; HUMAN; IMAGE ANALYSIS; IN VITRO STUDY; MALE; MEDICAL HISTORY; MICROGYRIA; MOLECULAR DYNAMICS; MOLECULAR PATHOLOGY; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; PHENOTYPE; POLYMERASE CHAIN REACTION; PRESCHOOL CHILD; WHOLE EXOME SEQUENCING; AMINO ACID SEQUENCE; ASIAN CONTINENTAL ANCESTRY GROUP; CONNECTIVE TISSUE; DEFICIENCY; ETHNOLOGY; EXOME; GENETICS; HIGH THROUGHPUT SEQUENCING; MEGALENCEPHALY; METABOLISM; MUSCLE HYPOTONIA; NUCLEOTIDE SEQUENCE; PATHOLOGY;

AMINO ACID SEQUENCE; ASIAN CONTINENTAL ANCESTRY GROUP; BASE SEQUENCE; CHILD, PRESCHOOL; CONNECTIVE TISSUE; EXOME; GENE EXPRESSION; GERM-LINE MUTATION; GROWTH HORMONE; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MALE; MEGALENCEPHALY; MUSCLE HYPOTONIA; PHENOTYPE; PROTO-ONCOGENE PROTEINS C-AKT;

EID: 85012891427     PISSN: 15524825     EISSN: 15524833     Source Type: Journal    
DOI: 10.1002/ajmg.a.38099     Document Type: Article

References (12)

1. Gai D, Haan E, Scholar M, Nicholl J, Yu S. 2015. Phenotypes of AKT3 deletion: A case report and literature review. Am J Med Genet Part A 167A:174–179.
2. Hussain K, Challis B, Rocha N, Payne F, Minic M, Thompson A, Daly A, Scott C, Harris J, Smillie BJ, Savage DB, Ramaswami U, De Lonlay P, O'Rahilly S, Barroso I, Semple RK. 2011. An activating mutation of AKT2 and human hypoglycemia. Science 334:474.
3. Jansen LA, Mirzaa GM, Ishak GE, O'Roak BJ, Hiatt JB, Roden WH, Gunter SA, Christian SL, Collins S, Adams C, Rivière JB, St-Onge J, Ojemann JG, Shendure J, Hevner RF, Dobyns WB. 2015. PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia. Brain 138:1613–1628.
4. Lee JH, Huynh M, Silhavy JL, Kim S, Dixon-Salazar T, Heiberg A, Scott E, Bafna V, Hill KJ, Collazo A, Funari V, Russ C, Gabriel SB, Mathern GW, Gleeson JG. 2012. De novo somaticmutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat Genet 44:941–945.
5. Mirzaa GM, Conway RL, Gripp KW, Lerman-Sagie T, Siegel DH, deVries LS, Lev D, Kramer N, Hopkins E, Graham JM Jr, Dobyns WB. 2012. Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: Two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis. Am J Med Genet Part A 158A:269–291.
6. Nakamura K, Kato M, Tohyama J, Shiohama T, Hayasaka K, Nishiyama K, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Matsumoto N, Saitsu H. 2014. AKT3 and PIK3R2 mutations in two patients with megalencephaly-related syndromes: MCAP and MPPH. Clin Genet 85:396–398.
7. Nellist M, Schot R, Hoogeveen-Westerveld M, Neuteboom RF, van der Louw EJ, Lequin MH, Bindels-de Heus K, Sibbles BJ, de Coo R, Brooks A, Mancini GM. 2015. Germline activating AKT3 mutation associated with megalencephaly, polymicrogyria, epilepsy and hypoglycemia. Mol Genet Metab 114:467–473.
8. Poduri A, Evrony GD, Cai X, Elhosary PC, Beroukhim R, Lehtinen MK, Hills LB, Heinzen EL, Hill A, Hill RS, Barry BJ, Bourgeois BF, Riviello JJ, Barkovich AJ, Black PM, Ligon KL, Walsh CA. 2012. Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron 74:41–48.
9. Rivière JB, Mirzaa GM, O'Roak BJ, Beddaoui M, Alcantara D, Conway RL, St-Onge J, Schwartzentruber JA, Gripp KW, Nikkel SM, Worthylake T, Sullivan CT, Ward TR, Butler HE, Kramer NA, Albrecht B, Armour CM, Armstrong L, Caluseriu O, Cytrynbaum C, Drolet BA, Innes AM, Lauzon JL, Lin AE, Mancini GM, Meschino WS, Reggin JD, Saggar AK, Lerman-Sagie T, Uyanik G, Weksberg R, Zirn B, Beaulieu CL, Majewski J, Bulman DE, O'Driscoll M, Shendure J, Graham JM Jr, Boycott KM, Dobyns WB. 2012. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet 44:934–940.
10. Takagi M, Shimizu M, Suzuki E, Shinohara H, Narumi S, Hasegawa T, Nishimura G, Hasegawa Y. 2016. Whole exome sequencing identified a novel COL2A1 mutation that causes mild Spondylo-epiphyseal dysplasia mimicking autosomal dominant brachyolmia. Am J Med Genet Part A 170A:795–798.
11. Wang D, Zeesman S, Tarnopolsky MA, Nowaczyk MJ. 2013. Duplication of AKT3 as a cause of macrocephaly in duplication 1q43q44. Am J Med Genet Part A 161A:2016–2019.
12. Wu C, Orozco C, Boyer J, Leglise M, Goodale J, Batalov S, Hodge CL, Haase J, Janes J, Huss JW 3rd, Su AI. 2009. BioGPS: An extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol 10:R130.