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

Masaki Takagi; Kazushige Dobashi; Keiko Nagahara; Mitsuhiro Kato; Gen Nishimura; Ryuji Fukuzawa; Satoshi Narumi; Tomonobu Hasegawa

doi:10.1002/ajmg.a.38099

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

Am J Med Genet A. 2017 Apr;173(4):1071-1076. doi: 10.1002/ajmg.a.38099. Epub 2017 Feb 12.

Authors

Masaki Takagi¹, Kazushige Dobashi², Keiko Nagahara², Mitsuhiro Kato², Gen Nishimura³, Ryuji Fukuzawa⁴, Satoshi Narumi^{1

5}, Tomonobu Hasegawa¹

Affiliations

¹ Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
² Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
³ Department of Radiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
⁴ Department of Pathology and Laboratory Medicine, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
⁵ Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.

PMID: 28190287
DOI: 10.1002/ajmg.a.38099

Abstract

Germline or somatic gain-of-function mutations in the v-akt murine thymoma viral oncogene homolog 3 (AKT3) have been reported to cause syndromic megalencephaly. We describe a novel germline mutation, p.Glu40Lys, in AKT3. Phenotypically, the patient presented with megalencephaly with hypotonia, apparent connective tissue laxity, and growth hormone (GH) deficiency. To our knowledge, this is the first instance of a patient with megalencephaly with GH deficiency, harboring a germline de novo mutation in AKT3. © 2017 Wiley Periodicals, Inc.

Keywords: AKT3; growth hormone deficiency; megalencephaly.

Publication types

Case Reports

MeSH terms

Amino Acid Sequence
Asian People
Base Sequence
Child, Preschool
Connective Tissue / metabolism
Connective Tissue / pathology
Exome
Gene Expression
Germ-Line Mutation*
Growth Hormone / deficiency*
Growth Hormone / genetics
High-Throughput Nucleotide Sequencing
Humans
Male
Megalencephaly / diagnosis
Megalencephaly / ethnology
Megalencephaly / genetics*
Megalencephaly / pathology
Muscle Hypotonia / diagnosis
Muscle Hypotonia / ethnology
Muscle Hypotonia / genetics*
Muscle Hypotonia / pathology
Phenotype
Proto-Oncogene Proteins c-akt / genetics*
Proto-Oncogene Proteins c-akt / metabolism

Substances

Growth Hormone
AKT3 protein, human
Proto-Oncogene Proteins c-akt