- Jul 2018
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europepmc.org europepmc.org
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On 2014 Nov 12, Musharraf Jelani commented:
Before becoming Martin et al (2014) article online we had submitted an eletter to J Med Genet, however we did not receive any response for it publishing it online. We want to share our comments as follows.
"PLK4: A novel candidate for primordial dwarfism?"
Letter to Editor Shaheen et al. 1 recently reported a homozygous 5 bps deletion mutation (c.12991303delTAAG; p.Phe433Leufs*6) in the human polo-like kinase 4 (PLK4,MIM 605031) gene and proposed that it is a compelling candidate for primordial dwarfism (PD). Autozygosity mapping and LOD score, method of estimating linkage distances, are adopted for the novel locus identification. Candidate gene hunting among 144 in the region is based on filtering through ToppGene suite 2. Mutation screening through Sanger sequencing of PLK4 gene is only based on ToppGene suite ranking. In this study authors have not mentioned how many and which samples were selected for genotyping and linkage analysis so the predicted maximum LOD score cannot be calculated. Maximum multipoint LOD score (2.5) obtained by the authors is quite lower than the established threshold values (3.0). In article it has been stated that all PD genes in training set in comparison to all 144 genes of the locus in test set were enrolled in ToppGene candidate prioritization. These genes lists must be provided along with test parameters. In our opinion these informations are essential for data reproducibility and validation. Only PLK4 gene has been selected for Sanger sequencing but The candidate region (Chr4:112904466-129392060, GRCh37/hg19) includes some of the well- known syndromes characterized by autosomal recessive intellectual disabilities, microcephaly, short stature, and overlapping phenotypes. Alazami syndrome caused by mutations in LARP7, autosomal recessive type 1 mental retardation caused by mutations in PRSS12, Bardet-Biedl syndrome caused by mutations in BBS7 and BBS12, Van Maldergem syndrome 2 caused by mutations in FAT4, neuronal ceroid lipofuscinosis 7 caused by mutations in MFSD8, a multisystem disorder including brain function caused by mutation in SCLT1, as well as genes involved in mitosis and brain development e.g. MAD2L1, FGF2, INTU, have not been discussed throughout the manuscript. Furthermore, chromatograms for obligate carriers have not been presented nor the Saudi population screening for minor allele frequency has been performed. Similarly a homozygous variant (NM014264.4, c.1556G>C; p.Trp519Ser) reported in ESP6500 (http://evs.gs.washington.edu/EVS/) alters a highly conserved amino acid of PLK4 however it has not been assigned to any of primordial dwarfism phenotype and not discussed by the authors. In fact, phenotypic overlaps among the study mutants and the above syndromes would be of far more value instead of paying an exaggerated attention to PLK4 biology. References
1 Shaheen R, Al Tala S, Almoisheer A et al. Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism. Journal of medical genetics 2014. 2 Chen J, Bardes EE, Aronow BJ et al. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic acids research 2009; 37: W305-11.
"conflict-of-interest" No conflict
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
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- Feb 2018
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europepmc.org europepmc.org
-
On 2014 Nov 12, Musharraf Jelani commented:
Before becoming Martin et al (2014) article online we had submitted an eletter to J Med Genet, however we did not receive any response for it publishing it online. We want to share our comments as follows.
"PLK4: A novel candidate for primordial dwarfism?"
Letter to Editor Shaheen et al. 1 recently reported a homozygous 5 bps deletion mutation (c.12991303delTAAG; p.Phe433Leufs*6) in the human polo-like kinase 4 (PLK4,MIM 605031) gene and proposed that it is a compelling candidate for primordial dwarfism (PD). Autozygosity mapping and LOD score, method of estimating linkage distances, are adopted for the novel locus identification. Candidate gene hunting among 144 in the region is based on filtering through ToppGene suite 2. Mutation screening through Sanger sequencing of PLK4 gene is only based on ToppGene suite ranking. In this study authors have not mentioned how many and which samples were selected for genotyping and linkage analysis so the predicted maximum LOD score cannot be calculated. Maximum multipoint LOD score (2.5) obtained by the authors is quite lower than the established threshold values (3.0). In article it has been stated that all PD genes in training set in comparison to all 144 genes of the locus in test set were enrolled in ToppGene candidate prioritization. These genes lists must be provided along with test parameters. In our opinion these informations are essential for data reproducibility and validation. Only PLK4 gene has been selected for Sanger sequencing but The candidate region (Chr4:112904466-129392060, GRCh37/hg19) includes some of the well- known syndromes characterized by autosomal recessive intellectual disabilities, microcephaly, short stature, and overlapping phenotypes. Alazami syndrome caused by mutations in LARP7, autosomal recessive type 1 mental retardation caused by mutations in PRSS12, Bardet-Biedl syndrome caused by mutations in BBS7 and BBS12, Van Maldergem syndrome 2 caused by mutations in FAT4, neuronal ceroid lipofuscinosis 7 caused by mutations in MFSD8, a multisystem disorder including brain function caused by mutation in SCLT1, as well as genes involved in mitosis and brain development e.g. MAD2L1, FGF2, INTU, have not been discussed throughout the manuscript. Furthermore, chromatograms for obligate carriers have not been presented nor the Saudi population screening for minor allele frequency has been performed. Similarly a homozygous variant (NM014264.4, c.1556G>C; p.Trp519Ser) reported in ESP6500 (http://evs.gs.washington.edu/EVS/) alters a highly conserved amino acid of PLK4 however it has not been assigned to any of primordial dwarfism phenotype and not discussed by the authors. In fact, phenotypic overlaps among the study mutants and the above syndromes would be of far more value instead of paying an exaggerated attention to PLK4 biology. References
1 Shaheen R, Al Tala S, Almoisheer A et al. Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism. Journal of medical genetics 2014. 2 Chen J, Bardes EE, Aronow BJ et al. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic acids research 2009; 37: W305-11.
"conflict-of-interest" No conflict
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-