My interests are primarily focused towards translational medicine, specifically the application of novel molecular approaches to the diagnosis of genetic disorders. To this end, my past interest at Baylor College of Medicine has been mainly focused toward the development of exon-targeted microarrays for the detection of copy number variations (CNVs) in genes specifically involved in neurodevelopmental disorders or known to infer a higher risk of inherited cancers. Here at the University of Chicago Genetics Services Laboratory, I contributed to the implementation and validation of an exon-targeted oligo-microarray to identify CNVs in genes involved in orphan genetic diseases. The availability of this platform, along with traditional sequence analysis, provides patients with comprehensive mutation analysis and also helps us elucidating the frequency of CNVs in these diseases. The use of high resolution microarrays also enables to precisely define the size of an imbalance allowing the sequences at the breakpoints to be investigated and ultimately infer mechanism through which CNVs arise.
In the future, I plan to explore the molecular diagnosis of monogenic diabetes using next-generation sequencing (NGS). Mutations in approximately 20 different genes are now known to cause monogenic diabetes, including maturity-onset diabetes of the young, neonatal diabetes and mitochondrial diabetes. Unlike other types of diabetes, monogenic diabetes is caused by a defect in a single gene and can often be treated with oral medications rather than life-long insulin therapy, making it a model of personalized medicine. Developing a NGS protocol for genetic testing for monogenic forms of diabetes will allow a more comprehensive, cost-efficient and rapid method of diagnosis leading to quicker and more effective treatment.
Keutel syndrome: report of two novel MGP mutations and discussion of clinical overlap with arylsulfatase E deficiency and relapsing polychondritis.
(2014 Apr) Am J Med Genet A
. 2014 Apr;164A(4):1062-8. doi: 10.1002/ajmg.a.36390. Epub 2014 Jan 23. 24458983
Analysis of ASPM in an ethnically diverse cohort of 400 patient samples: perspectives of the molecular diagnostic laboratory.
(2014 Apr) Clin Genet
. 2014 Apr;85(4):353-8. doi: 10.1111/cge.12172. Epub 2013 May 13. 23611254
Copy number analysis of NIPBL in a cohort of 510 patients reveals rare copy number variants and a mosaic deletion.
(2014 Mar) Mol Genet Genomic Med
. 2014 Mar;2(2):115-23. doi: 10.1002/mgg3.48. Epub 2013 Nov 14. 24689074
Two novel RAD21 mutations in patients with mild Cornelia de Lange syndrome-like presentation and report of the first familial case.
(2014 Mar) Gene
. 2014 Mar 10;537(2):279-84. doi: 10.1016/j.gene.2013.12.045. Epub 2013 Dec 27. 24378232
Prenatal diagnostic conundrum involving a novel ATP7A duplication.
(2013 Jul) Clin Genet
. 2013 Jul;84(1):97-8. doi: 10.1111/cge.12041. Epub 2012 Nov 14. 23151012
Large duplication in MTM1 associated with myotubular myopathy.
(2013 Mar) Neuromuscul Disord
. 2013 Mar;23(3):214-8. doi: 10.1016/j.nmd.2012.11.010. Epub 2012 Dec 28. 23273872
A partial MECP2 duplication in a mildly affected adult male: a putative role for the 3' untranslated region in the MECP2 duplication phenotype.
(2012) BMC Med Genet
. 2012 Aug 10;13:71. doi: 10.1186/1471-2350-13-71. 22883432
LCR-initiated rearrangements at the IDS locus, completed with Alu-mediated recombination or non-homologous end joining.
(2011 Jul) J Hum Genet
. 2011 Jul;56(7):516-23. doi: 10.1038/jhg.2011.51. Epub 2011 May 19. 21593745
Detection of clinically relevant exonic copy-number changes by array CGH.
(2010 Dec) Hum Mutat
. 2010 Dec;31(12):1326-42. doi: 10.1002/humu.21360. Epub 2010 Nov 2. 20848651
22q13.3 deletion syndrome: clinical and molecular analysis using array CGH.
(2010 Mar) Am J Med Genet A
. 2010 Mar;152A(3):573-81. doi: 10.1002/ajmg.a.33253. 20186804
Regional genomic instability predisposes to complex dystrophin gene rearrangements.
(2009 Sep) Hum Genet
. 2009 Sep;126(3):411-23. doi: 10.1007/s00439-009-0679-9. Epub 2009 May 16. 19449031
Molecular diagnosis of Duchenne/Becker muscular dystrophy: enhanced detection of dystrophin gene rearrangements by oligonucleotide array-comparative genomic hybridization.
(2008 Sep) Hum Mutat
. 2008 Sep;29(9):1100-7. doi: 10.1002/humu.20841. 18752307
Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster.
(2008 Jun) Nat Genet
. 2008 Jun;40(6):719-21. doi: 10.1038/ng.158. Epub 2008 May 25. 18500341
Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males.
(2006 Dec) Genet Med
. 2006 Dec;8(12):784-92. 17172942