Rare Variant on the Paternal Allele in a Patient With Silver-Russell Syndrome.

Silver-Russell syndrome (SRS) is a rare, well-recognized disorder characterized by growth restriction, including intrauterine and postnatal growth. Most SRS cases are caused by hypomethylation of the paternal imprinting center 1 (IC1) in chromosome 11p15.5 and maternal uniparental disomy in chromosome 7 (UPD7). Here, we report on a Chinese family with a 4 year old male proband presenting with low birth weight, growth retardation, short stature, a narrow chin, delayed bone age, and speech delays, as a result of a rare molecular etiology. Whole-exome sequencing was conducted, and a novel splicing variant, NM_000612.4: c.157+5G > A, was identified on the paternal allele. functional analysis by RT-PCR and Sanger sequencing revealed that the variant leads to an aberrant RNA transcript lacking exon 2. Our results further confirm the variant mediates SRS and expand the pathogenic variant and phenotypic spectrum of -mediated SRS. The results indicate that, beyond DNA methylation and UPD7 and variant tests, gene screening should also be considered for SRS molecular diagnoses.