RESUMEN
Autosomal recessive microcephaly is a rare clinical condition, which is characterized by reduced brain size that can be associated with delayed intellectual ability, developmental delay, and seizure. In this study, we describe two siblings with microcephaly: a 12-year-old girl with primary microcephaly, and a 7-year-old boy with secondary microcephaly, whose episodes of seizure and neurodevelopmental regression started at 6 years and 6 months of age, respectively. The interesting finding in these siblings was two different presentations of the same variant: one case with primary and one case with secondary microcephaly. Whole-exome sequencing was performed in order to identify causative variants in one family having two affected siblings with microcephaly. Confirmation of the identified variant in the ZNF335 gene in the proband and her affected brother and segregation analysis in the family were performed using the Sanger sequencing method. In both patients, a novel homozygous missense variant, [NM_022095.4: c.3346G>A; p.(Gly1116Arg)], in the ZNF335 gene was identified. The p.(Gly1116Arg) variant causes a defect in the last zinc finger domain of the protein. Conservation analysis by ConSurf server and UCSC genome browser revealed that Gly1116 is a highly conserved amino acid among different species. Different in-silico prediction tools and bioinformatics analysis predicted this variant as damaging.