Brief overview of the paper and its main findings

Na et. al. described a fetus with compound heterozygous mutations in the PIGN gene. The fetus was hypotonia-seizures syndrome. After ultrasound examination, the pregrancy was terminated due to the clinical findings. Exome sequencing was performed to the fetus and the findings were evaluated with Sanger sequencing and RT-PCR. Two rare variants that affect splicing of PIGN mRNA were detected in the fetus and the inheritance of the mutations fit into the autosomal recessive inheritance. Major and minor points The authors identified two splice affecting variants in a fetus. They provided evidence on how the novel splice site mutation affects the transcript by performing RT-PCR ans Sanger sequencing. More evidences for both mutation could have been included. - The two mutations reported here are rare variants observed in only East Asian populations. The authors used gnomAD as a population database but East Asian populations are not well represented in gnomAD. Can they provide allele frequencies of these variants from different databases as a table?

• More detailed clinical findings of the fetus should be described.
• The synonymous variant affects the splicing and this should be emphasized and highlighted.
• CADD scores and predictions from different in silico predicion programs should be included.
• Even though synonymous variant has reported previously, they could be able to check if it affects splicing.
• Have they confirmed their resuits in parents' RNA samples?
• Line 133-134, add reference and clarify the sentence. Where has it been reported previously?
• Change low carry rate to minor allele frequency
• Change "compund heterogenous" to "compound heterozygous"

Conflicts of interest

Do you have any conflicts of interest here? No