Mosaic variegated aneuploidy syndrome 2 with biallelic novel CEP57 splice site variation in Indian siblings: Expanding the clinical and molecular spectrum.

Mosaic variegated aneuploidy syndrome 2 (MVA2) (MIM# 614114) is a rare autosomal recessive condition caused by biallelic loss of function variants in the CEP57 gene. MVA2 is characterized by a variable phenotype ranging from poor growth to facial dysmorphism, short stature and congenital heart defects. Only 11 families and 5 pathogenic variants of MVA2 have been described so far. Intragenic duplication of 11 nucleotides (c.915_925dup11) in homozygous or compound heterozygous state is the commonest genetic aberration (10/13). We describe the first Indian family with two siblings with a novel homozygous splice site variant (c.382+2T>C) in CEP57. Molecular characterization demonstrated skipping of exon 3 due to the variant with protein modeling predicting subsequent complete loss of function. This is the first report of a splice site variation in CEP57 leading to MVA2.