HLX is a candidate gene for a pattern of anomalies associated with congenital diaphragmatic hernia, short bowel, and asplenia.
Sandra A FarrellSandi SodhiChristian R MarshallAndrea GuerinAnne SlavotinekTara PatonKaren ChongWilma L SirkinStephen W SchererFélix-Antoine Bérubé-SimardNicolas PilonPublished in: American journal of medical genetics. Part A (2017)
Isolated congenital diaphragmatic hernia is often a sporadic event with a low recurrence risk. However, underlying genetic etiologies, such as chromosome anomalies or single gene disorders, are identified in a small number of individuals. We describe two fetuses with a unique pattern of multiple congenital anomalies, including diaphragmatic hernia, short bowel and asplenia, born to first-cousin parents. Whole exome sequencing showed that both were homozygous for a missense variant, c.950A>C, predicting p.Asp317Ala, in the H.20-Like Homeobox 1 (HLX1) gene. HLX is a homeobox transcription factor gene which is relatively conserved across species. Hlx homozygous null mice have a short bowel and reduced muscle cells in the diaphragm, closely resembling the anomalies in the two fetuses and we therefore suggest that the HLX mutation in this family could explain the fetal findings.
Keyphrases
- copy number
- genome wide
- transcription factor
- genome wide identification
- gestational age
- skeletal muscle
- dna methylation
- gene expression
- intensive care unit
- type diabetes
- genome wide analysis
- late onset
- cell proliferation
- cell death
- mechanical ventilation
- insulin resistance
- preterm birth
- early onset
- preterm infants
- extracorporeal membrane oxygenation