Bi-allelic loss of function variants in SLC30A5 as cause of perinatal lethal cardiomyopathy.

Lieberwirth JK, Joset P, Heinze A, Hentschel J, Stein A, Iannaccone A, Steindl K, Kuechler A, Abou Jamra R

European journal of human genetics : EJHG 2021

Perinatal mortality is a heavy burden for both affected parents and physicians. However, the underlying genetic causes have not been sufficiently investigated and most cases remain without diagnosis. This impedes appropriate counseling or therapy. We describe four affected children of two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. In the four patients, we found the following homozygous loss of function (LoF) variants in SLC30A5 NM_022902.4:c.832_836del p.(Ile278Phefs*33) and NM_022902.4:c.1981_1982del p.(His661Tyrfs*10). Knockout of SLC30A5 has previously been shown a cardiac phenotype in mouse models and no homozygous LoF variants in SLC30A5 are currently described in gnomAD. Taken together, we present SLC30A5 as a new gene for a severe and perinatally lethal form of cardiomyopathy.

2 Figures Extracted

Fig. 1 PMC

Overview on individuals. The figure lists key information on all affected individuals including variant postions. The conventional symbols were used f...

Fig. 2 PMC

Imaging findings of the affected individuals. Prenatal ultrasound scans at the level of four-chamber view of individuals of family 1 ( A : Voluson S8,...