File:Microcephaly and short stature 01.jpg

DONSON mutations cause severe microcephaly and short stature

(a) Length at birth (Lgt), current height (Hgt) and head circumference (occipital frontal circumference; OFC) plotted as z-scores (s.d. from population mean for age and sex; SD). Black horizontal bars indicate mean values. Dashed line at –2 SD indicates cut-off for normal population distribution. Patients from the three independently identified DONSON patient cohorts are denoted by black (P1–P12 and P20, n = 16), orange (P13, n = 3) and blue (P14–P19 and P21, n = 10) circles. (b) Photographs of affected individuals with DONSON mutations demonstrating facial similarities. Written consent to publish photographs was obtained from the affected families. P, patient. (c) Schematics of the DONSON gene (top) and DONSON protein (bottom), indicating positions of the identified nucleotide mutations and amino acid substitutions, respectively. DONSON mutations comprised a range of mutation classes (nonsense, frameshift, essential splice site, missense and intronic). The genomic structure is based on the longest open reading frame (ORF), which contains ten coding exons (white rectangles) (NM_017613.3). The positions of identified mutations affecting splicing are shown on the gene structure (top), and the missense and truncating variants are shown on the encoded protein (bottom).

Reference

Reynolds, JJ etal., Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism. Nature Genetics (2017) doi:10.1038/ng.3790

http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3790.html

Copyright

Ng.3790-F1.jpg