Novel hemizygous loss-of-function variant in NONO identified in a South African boy

Am J Med Genet A. 2022 Jan;188(1):373-376. doi: 10.1002/ajmg.a.62509. Epub 2021 Sep 22.

Abstract

Hemizygous loss-of-function variants in the non-POU domain-containing, octamer-binding gene, NONO, cause X-linked mental retardation syndrome 34 (MRXS34). Here, we describe the 12th patient in the literature with this rare syndrome, the first affected male from sub-Saharan Africa. This South African patient presented with dysmorphic features, congenital cardiac abnormalities (Ebstein's anomaly, left ventricular non-compaction, and a VSD), and developmental delay. He was enrolled in our "Undiagnosed Disease Programme." Exome sequencing identified a novel hemizygous 14bp deletion in NONO, which he inherited from his unaffected, healthy mother. His features overlap with the previous patients described, lending more support to the assertion that MRXS34 is a recognizable, albeit rare, syndrome. The cardiac anomalies are particularly distinctive, which combined with a variety of other associated features, should prompt the inclusion of NONO-associated MRXS34 in the differential diagnosis.

Keywords: Ebstein's anomaly; MRXS34; NONO; South Africa; X-linked; whole-exome sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / genetics
  • Ebstein Anomaly* / diagnosis
  • Exome Sequencing
  • Heart Defects, Congenital* / complications
  • Heart Defects, Congenital* / diagnosis
  • Heart Defects, Congenital* / genetics
  • Humans
  • Intellectual Disability* / complications
  • Intellectual Disability* / diagnosis
  • Intellectual Disability* / genetics
  • Male
  • RNA-Binding Proteins / genetics
  • South Africa

Substances

  • DNA-Binding Proteins
  • NONO protein, human
  • RNA-Binding Proteins