Höfundar:
Helga Hauksdóttir, Kristján Ari Ragnarssson, Edda María Elvarsdóttir, Eirikur Briem, Jón Jóhannes Jónsson
Background/Objectives: A mother-daughter pair presented to our genetic clinic with an unusual phenotype of mild developmental delay, distal arthrogryposis, exostoses of manubrium sterni, missing adult teeth, and amblyopia. Chromosome analysis identified a de novo balanced reciprocal translocation t(7;22)(q36.2;q13.32) in the mother and inherited in daughter suggesting gene rearrangement. We characterized the patients with a novel cytogenetic technique to determine the breakpoints and identify a candidate gene.
Methods: Clinical laboratory genomics workup. Optical genome mapping (OGM) was performed at the Bionano Services Lab in France. For each sample, ultra-high molecular weight DNA was purified, labelled and stained. The Saphyr chip was ran on both samples aiming for at least 100X coverage. The de novo assembly and Variant Annotation pipelines were executed on Bionano Solve v3.7 and reporting and direct visualization of structural variants was done on Bionano Access v1.7.
Results: aCGH and short sequence WGS were negative. OGM was able to better define the breakpoints (ch22: 45,704,175.5 ± 2387.5bp. ch7: 155,867,681.5 ± 8,052.5bp) and revealed the potential involvement of one gene FAM118A.
Conclusion: We elucidated the breakpoints of this de novo translocation in patients which led to an identification of a candidate FM118A gene for a previously undescribed syndrome. The FAM118A gene encodes for an intramembrane protein with unknown biological function. It is not a known disease gene, but several possibly relevant associations with bone-related phenotypes have been reported. Further analysis is needed to determine molecular rearrangements in the FAM118A gene affecting pleiotropic effects.
Grant: Departmental service.
