Identification of a novel NF1 mutation in a Chinese family affected with neurofibromatosis type I / 中华医学遗传学杂志

OBJECTIVE@#To explore the molecular basis for a Chinese family affected with neurofibromatosis type I.@*METHODS@#Peripheral blood samples were collected from the proband and his parents. Potential mutations of NF1 gene were screened by PCR and Sanger sequencing. Pathogenicity of candidate mutations was analyzed using Polyphen-2 and Provean software.@*RESULTS@#Two mutations of the NF1 gene, including c.702G>A (synonymous mutation) and c.1733T>G (missense mutation), were discovered in the proband. Neither mutation was found in his parents and 50 healthy controls. Bioinformatics analysis indicated that the c.1733T>G mutation (p.Leu578Arg) was probably damaging. The affected codon L578 is highly conserved across various species.@*CONCLUSION@#The c.1733T>C mutation of the NF1 gene probably underlies the neurofibromatosis type I in this family.

Identification of de novo chromosomal structural abnormalities using whole genome sequencing / 中华医学遗传学杂志

OBJECTIVE To assess the value of whole genome sequencing for the identification of de novo structural chromosomal abnormalities. METHODS Whole genome sequencing was utilized to analyze a boy with a peripheral blood karyotype of 46,XY,ins(3)(q21p13p21). The patient manifested with ocular abnormalities including blepharophimosis and ptosis. RESULTS Whole genome sequencing suggested a fragmentation of chromosome 3 (from position 55 473 257 to 78 341 929) has been inserted into between 136 876 730 to 138 643 831, and the breakpoints have occurred in the intergenic region. Meanwhile, there was a deletion between 138 643 831 and 138 694 476. This region contains FOXL2, a pathogenic gene associated with blepharophimosis-ptosis-epicanthus inversus syndrome. CONCLUSION De novo structural chromosomal abnormalities may be caused by novel breakpoints or microdeletion flanking the deletion region. To confirm its pathogenic nature, a mutation needs to be assessed at both genetic and genomic levels, for which whole genome sequencing is a good option.

The value of blastocyst culture on preimplantation genetic diagnosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To estimate the value of blastocyst culture for preimplantation genetic diagnosis (PGD).</p><p><b>METHODS</b>Day 3 embryos were biopsied and analyzed with fluorescence in situ hybridization (FISH) technique. Embryos with normal FISH results were cultured into blastocysts, and the ones with better morphology scores were transferred. Fourteen embryos with abnormal FISH results were cultured into blastocysts. Part of the cells taken from the blastocysts were amplified by whole genomic amplification (WGA) and assessed by array-based comparative genomic hybridization (array-CGH) analysis.</p><p><b>RESULTS</b>Six blastocysts with normal FISH results were transferred in 5 cycles. Four healthy babies of 3 cycles were delivered. Another one was a singleton pregnancy but with embryo growth arrest, whose villus karyotype was normal. Fourteen embryos with abnormal FISH results were cultured into blastocysts and analyzed by array-CGH. Six blastocysts were normal by array-CGH.</p><p><b>CONCLUSION</b>FISH combined with blastocyst culture may further ensure the accuracy of PGD result. Detection at the blastocyst stage can avoid false positive results and mosaic interferences on Day 3 stage and are therefore more authentic.</p>