title: Avoiding pitfalls in molecular genetic testing: case studies of high-resolution array comparative genomic hybridization testing in the definitive diagnosis of Mowat-Wilson syndrome.
abstract: The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both cases was negative, but the application of high-resolution array comparative genomic hybridization technology lead to definitive diagnosis in both cases. We summarize the clinical findings and molecular testing in each case, discuss the differential diagnoses, and review the clinical and pathological findings of Mowat-Wilson syndrome. This report highlights the importance for those involved in molecular testing to know the nature of the underlying genetic abnormalities associated with the suspected diagnosis, to recognize the limitations of each testing platform, and to persistently pursue repeat testing using high-resolution technologies when indicated. This concept is applicable to both germline and somatic molecular genetic testing.
authors.affiliation: Departments of Laboratory Medicine, Neurology and Genetics, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Michael Joseph
authors.initials: MJ
authors.lastname: Kluk
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.forename: Philip
authors.initials: P
authors.lastname: James
authors.forename: David
authors.initials: D
authors.lastname: Coulter
authors.forename: David
authors.initials: D
authors.lastname: Harris
authors.forename: Bai-Lin
authors.initials: BL
authors.lastname: Wu
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000293:Adolescent; D002648:Child; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2; D055028:Comparative Genomic Hybridization; D019066:Facies; D005260:Female; D023061:Gene Order; D005820:Genetic Testing; D006627:Hirschsprung Disease / Q000175:diagnosis / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2