hi Salam,

have you considered testing for non paternity but with a genetically close partner possibly as a result of trying for a non affected child?

Hi Paul,

Thanks for your question. Yes, we have considered that but we have not done it yet. Theoretically this protein deficiency has protective effects against thrombosis, so parents don't even imagine they have a deleterious mutation. Even so, we and others already defined the haplotype of this mutation in more than 20 unrelated families, and all carriers have the same genetic markers (haplotype). So we still think it is an interesting case whether the mutation is from his parent or not, since there is a loss of the genetic markers of the mutation found. 

Morover, another curious thing, please find attached the pedigree, this rare case has two children with the same mutation as their mother but now they recover the haplotype of the mutation and have the same genteic markers as the grandfather as well as carriers from other families!! It seems like there are only somatic modifications not germline gene editing...although this is not a case of cancer research.

hi Salam,

as you have done NGS the data for paternity testing at other loci should be available in large amounts. Regarding crossovers within a short distance  that is unlikely in one patient but as you have sequenced over 20 patients/families you must multiply the genesize by the number of individuals giving many thousand of bases so the likelihood of a crossover must increase for any one random individual. I am really struggling with the pedigree, however, and cannot account for recovery of the haplotype without another crossover in the same family and this is extremely unlikely but hopefully someone will come up with an answer

Dear Salam

SNP Chip is the best method for detect of LOH

Best wishes

Mohammad Amin

Dear Paul, thanks for your time and contribution, this case is really very intriguing, I hope as well someone come up with an answer!!!

Hi Mohammad Amin, 

Thanks for your answer, we have already saw LOH by NGS and validated by Sanger...

Best,

sAlam

hi Salam,

if the samples in generation 2 and 3 were mixed up while taking blood or dna prep ( similar names perhaps) you would only need one recombination to make sense of the results. Other markers on unlinked genes/areas from you NGS data would test this possibility

Dear Salam,

Loss of heterozygosity and copy number decay could indicate deletion in one haplotype.