Prenatally diagnosed distal 16p11.2 microdeletion with a novel association with congenital diaphragmatic hernia: a case report

Abstract

A prenatal case presenting with congenital diaphragmatic hernia (CDH) and distal 16p11.2 microdeletion suggests two possible causative hypotheses: (1) a functional effect of chromatin loopings between the distal and the proximal 16p11.2 microdeletion traits, associated with CHD; (2) a possible role of ATP2A1, a deleted gene involved in diaphragm development.

Keywords: 16p11.2 deletion syndrome; array‐CGH analysis; congenital diaphragmatic hernia; prenatal diagnosis; ultrasound fetal anomalies.

Figure 1

Ultrasound examination at 18 gestational weeks. The stomach (ST) was herniated in left hemithorax with the hearth (H) in dextroposition. A little of small bowel (*) herniated through the defect also was present in thorax.

Figure 2

(A) High‐resolution array‐CGH analysis showing a ~220 kb‐microdeletion in the 16p11.2 region from 28,833,437 bp to 29,046,252 bp [hg19]. (B) This region encompasses nine known protein‐coding genes: ATXN2L, TUFM, SH2B1, ATP2A1, RABEP2, CD19, NFATC2IP, SPNS1, LAT, and the hsa‐MiR‐4517. Copy number variations were classified according to the Database of Genomic Variants (http://dgv.tcag.ca/dgv/app/home), the Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources (http://decipher.sanger.ac.uk/), and the UCSC Genome Browser (http://genome.ucsc.edu/cgi-bin/hgGateway). (C) FISH analysis with the Agilent SureFISH 16p11.2 ATXN2L‐LAT probe (Agilent Technologies Inc. Santa Clara, CA) mapping to the deleted 16p11.2 region (red signal). Centromeric probe for chromosome 16 was used as control probe (green signal). Only one red signal was detected in each metaphase of the proband, thus confirming the array‐CGH result. White arrow indicates the deleted chromosome.