32. Contemporary significance of cytogenetic results from decades-old fibroblasts

      Reanalysis of digital information such as chromosome microarrays and next-generation sequencing data has made increasing contributions to new diagnoses. We describe the re-analysis of cells banked with the consent of proactive parents over 20 years ago, impacting counseling and peace of mind for the proband's sibling. In 1997, a prenatal ultrasound identified multiple fetal anomalies: cleft lip and palate, contractures of the upper and lower extremities, agenesis of the corpus callosum and a congenital heart defect. An amniocentesis performed at an outside hospital reported a normal 46,XY karyotype. The infant was born at 38 weeks to a 36-year-old G3P0020 mother and, in view of the life limiting prognosis of the constellation of birth defects, comfort care was implemented. The infant survived at home for 83 days, and shortly after expiration, a skin biopsy was obtained. An autopsy identified the heart defect as tricuspid atresia, intact ventricular septum, and hypoplastic right ventricle. Frozen fibroblasts were thawed and cultured 21 years later. Chromosome microarray analysis was performed on DNA from these cells, identifying a 13.810 Mb loss involving 3p13p14 encompassing 66 genes [3p12.3p14.2(63296306_77106695)x1]. Interstitial deletions of 3p13p14 represent a rare, recurrent chromosomal alteration without a common critical region, with over 40 cases reported to date (sizes ranging 0.498 to >27 Mb). Common phenotypes include developmental delay, intellectual disability, autism, craniofacial dysmorphism and limb abnormalities. Multiple parental structural rearrangements leading to interstitial 3p deletions have been reported. We performed karyotype and metaphase FISH studies on peripheral blood from both parents alongside the proband's fibroblasts regrown in the lab. Using this fibroblast culture to establish the de novo status of this variant provided irreplaceable information for the counseling of his childbearing age sibling two decades later.
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