A strong founder effect for two NLRP7 mutations in the Indian population: an intriguing observation

Comprehensive genotype–phenotype correlations betweenNLRP7mutations and the balance between embryonic tissue differentiation and trophoblastic proliferation

“…Patients were referred to our laboratory from various national and international collaborators for DNA testing. All the patients have been screened for NLRP7 mutations as previously described,18 and the results of their mutation analysis were either previously reported18 20 33 34 46 or generated during this study and are described in the ‘Results' section and online supplementary table I.…”

Report of four new patients with protein-truncating mutations in C6orf221/KHDC3L and colocalization with NLRP7

“…Similarly, we previously reported the presence of several founder mutations in NLRP7 in the Indian, Chinese and Pakistani populations based on haplotype analyses. 10 Also, along with others, we previously reported the presence of the same rearrangement and missense in unrelated patients from Egypt and Mexico, respectively. 23,28 Re-reviewing SNPs in the sequenced NLRP7 amplicons in our patients and in those found in patients with identical mutations, reported by our collaborators, revealed more shared haplotypes, not only in patients from regions with high rate of consanguinity, but also in patients from different populations.…”

“…NLRP7 is mutated in 88% and 60% of analyzed familial and singleton cases of RHMs, respectively. [9][10][11][12][13][14] Recently, we demonstrated that ex vivo lipopolysaccharides (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) from patients with mutations and rare variants in NLRP7 have defective interleukin-1 beta (IL-1b) and tumor necrosis factor secretion but normal to higher intracellular levels of pro-and mature-IL-1b. 13,15 The requirement of NLRP7 for normal IL-1b secretion by macrophages was also confirmed in in vitro studies after NLRP7 silencing using small interfering RNA (siRNA).…”

Mutations inNLRP7are associated with diploid biparental hydatidiform moles, but not androgenetic complete moles

“…The major gene involved in this condition has been identified as NLRP7 and to date most cases of recurrent BiCHM, defined as two or more related women with recurrent CHM or a single woman with recurrent BiCHM, have been found to be homozygous or compound heterozygotes for nonsense mutations or pathological non-synonymous variants in NLRP7 9–16 18 29. A small number of further cases have been described in which single individuals have a reproductive history compatible with recurrent BiCHM and are homozygous or compound heterozygotes for mutations or pathological variants in NLRP7 , but in whom the origin of the CHM have not been reported9 10 13 15 17 19–21 29 and are likely to represent further cases of women with BiCHM.…”

“…However, in many cases with recurrent BiCHM, nonsense mutations have not been identified in the gene. Instead, affected individuals have been found to be homozygous for non-synonymous variants of NLRP7 not found in control individuals,9 11–13 15 17 suggesting that these variants are involved in the pathology of recurrent BiCHM. A small number of individuals are compound heterozygotes for a protein truncating mutation together with a non-synonymous variant 10 12 18…”