Necrotizing Enterocolitis in Two Siblings and an Unrelated Infant with Overlapping Chromosome 6q25 Deletions

Abstract

The pathogenesis of necrotizing enterocolitis (NEC) remains poorly understood but is thought to be multifactorial. There are no specific recurring chromosomal abnormalities previously associated with NEC. We report 3 cases of intestinal necrosis associated with large chromosome 6 deletions. The first patient was found to have a 7.9-Mb deletion of chromosome 6 encompassing over 40 genes, arr[GRCh37] 6q25.3q26(155699183_163554531)×1. The second patient had a 19.5-Mb deletion of chromosome 6 generated by an unbalanced translocation with chromosome 18, 46,XY,der(6)t (6;18)(q25.1;p11.23), arr[GRCh37] 6q25.1q27(151639526_ 171115067)×1, 18p11.32p11.23(131700_7694199)×3, which included the whole 7.9-Mb region deleted in the first patient. The third patient was the younger sibling of the second patient with an identical derivative chromosome 6. The shared abnormal chromosome 6 region includes multiple genes of interest, particularly EZR. Mouse models have demonstrated that Ezr is expressed in microvillar epithelium and helps regulate cell-cell adhesion in the gut. We hypothesize that deletion of this shared region of 6q leads to gastrointestinal vulnerability which may predispose patients to intestinal necrosis.

Non‐occlusive mesenteric ischemia in a toddler with 6q25 microdeletion syndrome

“…To the best of our knowledge, this is the first case of NOMI diagnosed by clinical and histopathological findings in a pediatric patient with interstitial 6q25 microdeletion syndrome. Regarding the reports of intestinal inflammation in patients with Coffin–Siris or 6q25 microdeletion syndrome, three cases of necrotizing enterocolitis in children with chromosome 6q25 deletions have been reported 4 . The authors speculated that the EZR gene, which was also deleted in this patient, can be a predisposing factor of intestinal vulnerability.…”

Major Chromosomal Abnormalities and Necrotizing Enterocolitis: Is there a Link?

“…Chromosome 6: NEC-like intestinal necrosis had been described in two infants and in one neonate that was full-term or near fullterm born by Esdal et al 16 All three cases shared a deletion on chromosome 6 in the region 6q25.3 to q26. One of the infants had a deletion on chromosome 6, while one of the infants and the neonate were siblings and had identical unbalanced chromosome 6 to chromosome 18 translocations resulting in the loss of genetic material from chromosome 6.…”

Comparison and Investigation of Exosomes from Human Amniotic Fluid Stem Cells and Human Breast Milk in Alleviating Neonatal Necrotizing Enterocolitis

“…These results indicated that HBM-exos were more focused on regulating biological processes of growth and development. It has been documented that genetic variation in chromosomes is associated with an increased risk of NEC [ 37 , 38 ]. Our results and those of previous studies indicate that HBM-exos have good prospects for NEC caused by genetic metabolism or abnormal growth and development.…”