A rare example of germ-line chromothripsis resulting in large genomic imbalance

作者：Anderson Sarah E^*; Kamath Arveen; Pilz Daniela T; Morgan Sian M

来源：Clinical Dysmorphology, 2016, 25(2): 58-62.

DOI：10.1097/MCD.0000000000000113

• chromoanasynthesis
• chromothripsis
• complex genomic rearrangements
• distal 13q deletions
• X inactivation

Chromothripsis is a recently described chromosome catastrophe' phenomenon in which multiple genomic rearrangements are generated in a single catastrophic event. Chromothripsis has most frequently been associated with cancer, but there have also been rare reports of chromothripsis in patients with developmental disorders and congenital anomalies. In contrast to the massive DNA loss that often accompanies chromothripsis in cancer, only minimal DNA loss has been reported in the majority of cases of chromothripsis that have occurred in the germ line. Presumably, this is because in most instances, large genomic losses would be lethal in utero. We report on a female patient with developmental delay and dysmorphism. G-banded chromosome analysis detected a subtle, interstitial deletion of chromosome 13 and a complex rearrangement of one X chromosome. Subsequent array comparative genomic hybridisation studies indicated nine deletions on the X chromosome ranging from 327kb to 8Mb in size. A 4.4Mb deletion on chromosome 13 was also confirmed, compatible with the patient's clinical phenotype. We propose that this is a rare example of constitutional chromothripsis in association with relatively large genomic imbalances and that these have been tolerated in this case as they have occurred in a female on the X chromosome, which has undergone preferential X inactivation.

• 出版日期2016-4
• 单位河北医科大学