NSMCE2 / MMS21 structural variant causes chromosome breakage syndrome with primordial dwarfism and severe lung disease.
Tomer Poleg, Noam Hadar, Vadim Dolgin et al.
✦ AI-curated · Sources linked
Case in brief
Two siblings of non-consanguineous Indian-Jewish ancestry had severe postnatal growth restriction, hypotonia, characteristic facial features, hypothyroidism, late-onset insulin-dependent diabetes, borderline immune dysregulation, and recurrent pneumonia with interstitial lung disease. Both died in adolescence. Karyotype and microarray results were normal, but stimulated lymphocytes showed spontaneous chromosome breakage and polyploidy without hypersensitivity to cross-linking agents. Genome analysis identified a homozygous tandem duplication in NSMCE2; RNA studies confirmed an aberrant transcript predicted to truncate the protein and remove its SUMO domain.
What made this case unusual
The syndrome combined primordial dwarfism and spontaneous chromosome breakage with severe interstitial lung disease, alongside immune-endocrine abnormalities and adolescent lethality.
Diagnostic / clinical pearl
Normal karyotype and microarray results did not exclude a chromosome breakage syndrome: cytogenetic testing of stimulated lymphocytes revealed spontaneous breakage and polyploidy, while structural-variant analysis identified the NSMCE2 duplication.