Two novel TSC2 frameshift mutations in tuberous sclerosis complex / 中国当代儿科杂志

High-throughput sequencing was performed for the peripheral blood DNA from two probands in the family with tuberous sclerosis complex (TSC) to determine the sequences of TSC-related genes TSC1 and TSC2 and their splicing regions and identify mutation sites. Amplification primers were designed for the mutation sites and polymerase chain reaction and Sanger sequencing were used to verify the sequences of peripheral blood DNA from the probands and their parents. The two probands had c.3981-3982 insA (p.Asp1327AspfsX87) and c.4013-4014 delCA (p.Ser1338Cysfs) heterozygous mutations, respectively, in the TSC2 gene. The parents of proband 1 had no abnormalities at these two loci; the mother of proband 2 had c.4013-4014 delCA heterozygous mutation in the TSC2 gene, while the father and the grandparents of proband 2 had no abnormalities. c.3981-3982 insA mutation may cause early coding termination of amino acid sequence at the 1413th site, and c.4013-4014 delCA mutation may cause early coding termination of amino acid sequence at the 1412th site. These two mutations are the pathogenic mutations for families 1 and 2, respectively, and both of them are novel frameshift mutations, but their association with the disease needs to be further verified by mutant protein function cell model and animal model.

Analysis of copy number variations in an infant with Cri du Chat syndrome by array-based comparative genomic hybridization / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze genomic copy number variations in an infant with Cri du Chat syndrome, and to explore the underlying genetic cause.</p><p><b>METHODS</b>G-banding analysis was carried out on cultured peripheral blood sample from the patient. Copy number variation analysis was performed using microarray comparative genomic hybridization, and the result was verified with fluorescence in situ hybridization.</p><p><b>RESULTS</b>The infant was found to have a 46, XY, der(5) (p?) karyotype. By microarray comparative genomic hybridization, a 23.263 Mb deletion was detected in 5p14.2-p15.3 region in addition to a 14.602 Mb duplication in 12p31 region. A derivative chromosome was formed by rejoining of 12p31 region with the 5p14.2 breakpoint. The patient therefore has a karyotype of arr cgh 5p15.3p14.2 (PLEKHG4B>CDH12)× 1 pat, 12p13.33p13.1 (IQSEC3>GUC Y2C)× 3 pat. Loss of distal 5p and gain of distal 12p were verified with fluorescence in situ hybridization.</p><p><b>CONCLUSION</b>The Cri du Chat syndrome manifested by the patient was caused by deletion of distal 5p from an unbalanced translocation involving chromosome 5. Microarray comparative genomic hybridization is a powerful tool for revealing genomic copy number variations for its high-resolution, high-throughput and high accuracy.</p>

Clinical significance of large-scale screening of A1555G mutation of mitochondria DNA for neonates / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the necessity of large-scale screening of mitochondria DNA (mtDNA) A1555G mutation for prevention of aminoglycoside antibiotic induced deafness in newborns.</p><p><b>METHODS</b>One thousand blood filter samples were collected from neonates born in July 2008 in Shenzhen. DNA was extracted with Chelex-100 Resin and amplified by PCR. The mtDNA A1555G mutation was determined by denaturing high-performance liquid chromatography(DHPLC) for PCR products. The positive frequency was calculated.</p><p><b>RESULTS</b>The mitochondrial DNA A1555G mutation was detected in 2 cases of 1000 neonates. The frequency of mutation was 0.2%.</p><p><b>CONCLUSION</b>There is a high frequency of mtDNA A1555G mutation in neonates, the large-scale screening of mtDNAA1555G mutation in newborns might detect the individuals sensitive to aminoglycoside antibiotic, which is helpful to guide a rational medication for newborns and the maternal relatives at high-risk. Furthermore, it might be useful to prevent aminoglycoside antibiotic induced deafness.</p>

Molecular and prenatal diagnosis for a Chinese pregnant woman with a novel mutation of β thalassemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To conduct molecular and prenatal diagnosis for a couple with β thalassemia.</p><p><b>METHODS</b>Blood routine examination and hemoglobin analysis were used for screening of thalassemia. Seventeen common Chinese mutations of β thalassemia were detected for the carriers with β thalassemia using PCR/RDB. The unknown mutation of β thalassemia was identified by DNA sequencing and DHPLC analysis.</p><p><b>RESULTS</b>The husband was heterozygote of CD41/42 (-TCTT). The wife carried a mutation IVS-I-110 (G→A) of β thalassemia having not been reported in Chinese so far. The fetus was a double mutated heterozygote of IVS-I-110 (G→A) and CD41/42 (-TCTT). The pregnancy was terminated.</p><p><b>CONCLUSION</b>Mutation IVS-I-110 (G→A) of β thalassemia in Chinese is of importance to the genetic counseling and prenatal diagnosis of thalassemia.</p>