Abrams AJ, Hufnagel RB, Rebelo A, Zanna C, Patel N, Gonzalez MA, Campeanu IJ, Griffin LB, Groenewald S, Strickland AV, Tao F, Speziani F, Abreu L, Schule R, Caporali L, La Morgia C, Maresca A, Liguori R, Lodi R, Ahmed ZM, Sund KL, Wang X, Krueger LA, Peng Y, Prada CE, Prows CA, Schorry EK, Antonellis A, Zimmerman HH, Abdul-Rahman OA, Yang Y, Downes SM, Prince, J, Fontanesi F, Barrientos A, Nemeth AH, Carelli V, Huang T, Zuchner S, Dallman JE. Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder. Nat Genet. 2015 Aug;47(8):926-32.
This paper elucidates the molecular mechanism of disease in a Cincinnati Children's family and three additional families studied by other investigators afflicted with both optic atrophy and peripheral neuropathy. The gene identified encodes a transporter linked to mitochondrial dynamics. Further study of this gene in a mouse model is ongoing at Cincinnati Children's.
Hufnagel RB, Zimmerman SL, Krueger LA, Bender PL, Ahmed ZM, Saal HM. A new frontonasal dysplasia syndrome associated with deletion of the SIX2 gene. Am J Med Genet A. 2016 Feb;170A(2):487-91.
In this paper, a family with a craniofacial malformation in mother and daughter showed to have a chromosome deletion that included the SIX2 gene. While mouse models had previously shown a relationship between this malformation and the SIX2 gene, this was the first human family identified. This paper expands the number of genes associated with this specific craniofacial malformation. Translation of this knowledge should improve the diagnostic yield of molecular genetic panels.
Kang E, Wang X, Tippner-Hedges R, Ma H, Folmes CD, Gutierrez NM, Lee Y, Van Dyken C, Ahmed R, Li Y, Koski A, Hayama T, Luo S, Harding CO, Amato P, Jensen J, Battaglia D, Lee D, Wu D, Terzic A, Wolf DP, Huang T, Mitalipov S. Age-Related Accumulation of Somatic Mitochondrial DNA Mutations in Adult-Derived Human iPSCs. Cell Stem Cell. 2016 May;18(5):625-36.
This study showed that induced pluripotent stem cells (IPSCs), particularly those isolated from older individuals, could have mutations in mitochondrial DNA that impact the function of mitochondria in cells with higher mutation load. Since IPSCs are of interest for therapeutic purposes, this paper suggests screening these cell lines for mitochondrial mutations before therapeutic use.
Prada CE, Hufnagel RB, Hummel TR, Lovell AM, Hopkin RJ, Saal HM, Schorry EK. The Use of Magnetic Resonance Imaging Screening for Optic Pathway Gliomas in Children with Neurofibromatosis Type 1. J Pediatr. 2015 Oct;167(4):851-856.
Children with neurofibromatosis type 1 ( NF1) are at risk for optic pathway tumors. There has not been a consensus as to how often MRIs need done to ascertain risk for these tumors, and whether these patients are at risk for vision loss. This paper describes MRI findings in the very large NF1 cohort followed at Cincinnati Children's over 20 years and helps to define the age for new risk of tumor development as well as MRI features that predict health consequences. This data will help refine protocols for tumor surveillance in young children with NF1.
Zhang G, Bacelis J, Lengyel C, Teramo K, Hallman M, Helgeland O, Johansson S, Myhre R, Sengpiel V, Njolstad PR, Jacobsson B, Muglia L. Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis. PLoS Med. 2015 Aug 18;12(8):e1001865.
This paper reports the analysis of family cohorts and the impact of genetics as opposed to the fetal environment on fetal growth and gestational age. Researchers have long known that taller mothers have bigger babies, and the assumption has been that this effect is mainly a function of “room to grow”. This paper shows that fetal growth is an outcome of fetal growth genes. This information will inform future work on optimizing fetal growth and prevention of prematurity.