Molecular characteristics

Two point mutations have been identified in female LSDMCA3 cases, i.e., 262C>T and c.402delG. These mutations are predicted to lead to the introduction of a premature stop codon and to a frameshift, respectively. The latter mutation (p.Arg134Serfs∗3) was identified in a patient, a severely malformed fetus and their healthy mother and was also identified in patients with histiocytoid cardiomyopathy without skin manifestations. A hemizygous mutations c.361G>A:p.E121K was identified in a severe case of mitochondrial complex I deficiency. A recurring mutation, c.276_278del, p.F93del, has been identified in male cases of congenital sideroblastic anemia. Finally two de novo hemizygous variants (c.286C>T and c.328C>T) were described in two male patients with lactic acidosis, hypertrophic cardiomyopathy and isolated complex I deficiency. Notably all females carry a loss-of- function heterozygous variant, whereas males carry hemizygous missense or in-frame deletion indicating that residual activity of NDUFB11 is needed for males to be viable.