On 2017 Aug 02, Han-Xiang Deng commented:

We recently reported mutations in TMEM230 in familial Parkinson’s disease (PD). Farrer et al raised the concern that mutations in TMEM230 may not be pathogenic to PD. We seriously evaluated Dr. Farrer’s assertions. We obtained updated clinical information and performed several new experiments, including MegaEx chip screening of the family DNA samples with ~2 million SNPs for whole-genome linkage study and re-analysis of whole-exome sequencing data. We did not find any other locus more robust than the chromosome 20p (TMEM230), nor any other variants with better segregation than TMEM230-R141L to explain the inheritance of PD in the large Mennonite family. Based on the new genetic data from the Mennonite PD family, and the robust genetic data showing additional TMEM230 mutations in multiple PD families, we are confident to conclude that TMEM230 is a new PD-causing gene. Further studies of TMEM230 should provide important mechanistic insights into understanding the vesicle/endosome trafficking/recycling defects in the pathogenesis of PD. A detailed response is available in bioRxiv (http://www.biorxiv.org/content/early/2017/07/31/170852).

On 2016 Dec 31, MATTHEW FARRER commented:

We argue that TMEM230 mutations are neither disease-linked nor impair synaptic vesicle trafficking. Analysis of chromosome 20 STR genotyping, and of nucleotide mutations, in the largest Mennonite kindred shows the work by Deng and colleagues is erroneous. A detailed critique is available in bioRxiv (http://biorxiv.org/content/early/2017/01/01/097030). We recommend further assessment of genotype analysis/original samples (available on request) prior to embarking on TMEM230 biology. We caution that TMEM230 results are unlikely to contribute to a molecular understanding of parkinsonism.

On 2016 Dec 31, MATTHEW FARRER commented:

We argue that TMEM230 mutations are neither disease-linked nor impair synaptic vesicle trafficking. Analysis of chromosome 20 STR genotyping, and of nucleotide mutations, in the largest Mennonite kindred shows the work by Deng and colleagues is erroneous. A detailed critique is available in bioRxiv (http://biorxiv.org/content/early/2017/01/01/097030). We recommend further assessment of genotype analysis/original samples (available on request) prior to embarking on TMEM230 biology. We caution that TMEM230 results are unlikely to contribute to a molecular understanding of parkinsonism.

On 2017 Aug 02, Han-Xiang Deng commented:

We recently reported mutations in TMEM230 in familial Parkinson’s disease (PD). Farrer et al raised the concern that mutations in TMEM230 may not be pathogenic to PD. We seriously evaluated Dr. Farrer’s assertions. We obtained updated clinical information and performed several new experiments, including MegaEx chip screening of the family DNA samples with ~2 million SNPs for whole-genome linkage study and re-analysis of whole-exome sequencing data. We did not find any other locus more robust than the chromosome 20p (TMEM230), nor any other variants with better segregation than TMEM230-R141L to explain the inheritance of PD in the large Mennonite family. Based on the new genetic data from the Mennonite PD family, and the robust genetic data showing additional TMEM230 mutations in multiple PD families, we are confident to conclude that TMEM230 is a new PD-causing gene. Further studies of TMEM230 should provide important mechanistic insights into understanding the vesicle/endosome trafficking/recycling defects in the pathogenesis of PD. A detailed response is available in bioRxiv (http://www.biorxiv.org/content/early/2017/07/31/170852).