Analysis of P gene variations among fourteen patients with oculocutaneous albinism type Ⅱ / 中华医学遗传学杂志

Objective@#To analyze variations of TYR and P genes among 14 patients with clinically diagnosed oculocutaneous albinism.@*Methods@#Potential variations of the TYR and P genes were detected by Sanger sequencing. Novel variations were predicted with bioinformatics software including SIFT and PolyPhen-2.@*Results@#No variation was found in the TYR gene, while 9 types of variations were found in the P gene among the 14 patients, which included c. 803-3C>G (7/26), c. 1327G>A (p.Val443Ile) (5/26), c. 632C>T (p.Pro211Leu) (4/26), c. 1832T>C (p.Leu611Pro) (3/26), c. 1349C>A (p.Thr450Lys) (2/26), c. 2363C>T (p.Ser788Leu) (2/26), c. 2228C>T (p.Pro743Leu) (1/26), c. 1525A>G(p.Thr509Ala) (1/26), and c. 1349C>T(p.Thr450Met) (1/26). Only 1 heterozygous variation was detected in 2 families. c. 2363C>T (p.Ser788Leu), c. 1832T>C (p.Leu611Pro) and c. 1525A>G (p.Thr509Ala) were not reported previously and predicted as "harmful" to the protein function.@*Conclusion@#The main type of ocular albinism is oculocutaneous albinism type Ⅱ in Liuzhou region, where the most common variations of the P gene were c. 803-3C>G and c. 1327G>A (p.Val443Ile). Above finding has enriched the variation spectrum of the P gene.

SLC22A5 gene mutation analysis and prenatal diagnosis for a family with primary carnitine deficiency / 中华医学遗传学杂志

OBJECTIVE@#To carry out mutation analysis and prenatal diagnosis for a family affected with primary carnitine deficiency.@*METHODS@#Genomic DNA of the proband was extracted from peripheral blood sample 10 days after birth. The 10 exons and intron/exon boundaries of the SLC22A5 gene were subjected to PCR amplification and Sanger sequencing. The proband's mother was pregnant again two years after his birth. Fetal DNA was extracted from amniocytes and subjected to PCR and Sanger sequencing.@*RESULTS@#Tandem mass spectrometric analysis of the proband revealed low level of plasma-free carnitine whilst organic acids in urine was normal. Compound heterozygous SLC22A5 mutations c.1195C>T (inherited from his father) and c.517delC (inherited from his mother) were detected in the proband. Prenatal diagnosis has detected no mutation in the fetus. The plasma-free carnitine was normal after birth.@*CONCLUSION@#Appropriate genetic testing and prenatal diagnosis can prevent further child with carnitine deficiency. The identification of c.517delC, a novel mutation, enriched the spectrum of SLC22A5 mutations.

Clinical and genetic analysis of a child with Noonan syndrome / 中华医学遗传学杂志

OBJECTIVE@#To identify potential mutation in a child clinically diagnosed as Noonan syndrome and to provide genetic counseling and prenatal diagnosis for his family.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the patient and his parents, and amniotic fluid was taken from the mother during the second trimester. Next generation sequencing (NGS) was used to screen potential mutations from genomic DNA. Suspected mutation was verified by Sanger sequencing.@*RESULTS@#A heterozygous c.4A>G (p.Ser2Gly) mutation of the SHOC2 gene was identified in the patient but not among other family members including the fetus.@*CONCLUSION@#The Noonan syndrome is probably caused by the c.4A>G mutation of the SHOC2 gene. NGS is helpful for the diagnosis of complicated genetic diseases. SHOC2 gene mutation screening is recommended for patient suspected for Noonan syndrome.

Analysis of TRPM6 gene variant in a pedigree affected with hypocalcemia secondary to hypomagnesemia / 中华医学遗传学杂志

OBJECTIVE@#To explore the molecular pathogenesis for a pedigree affected with hypocalcemia secondary to hypomagnesemia.@*METHODS@#Sanger sequencing was used to detect potential variant of the TRPM6 gene in the patient and their parents.@*RESULTS@#The results showed that the patient has carried novel homozygous c.3311C>T (p.Pro1104Leu) variant of the TRMP6 gene, for which both of his parents were heterozygous carriers. Analysis of protein functions using software predicted high risk of pathogenicity.@*CONCLUSION@#The homozygous c.3311C>T (p.Pro1104Leu) variant of the TRPM6 gene probably underlies the disease in this patient.

Analysis of P gene variations among fourteen patients with oculocutaneous albinism type II / 中华医学遗传学杂志

OBJECTIVE@#To analyze variations of TYR and P genes among 14 patients with clinically diagnosed oculocutaneous albinism.@*METHODS@#Potential variations of the TYR and P genes were detected by Sanger sequencing. Novel variations were predicted with bioinformatics software including SIFT and PolyPhen-2.@*RESULTS@#No variation was found in the TYR gene, while 9 types of variations were found in the P gene among the 14 patients, which included c.803-3C>G (7/26), c.1327G>A (p.Val443Ile) (5/26), c.632C>T (p.Pro211Leu) (4/26), c.1832T>C (p.Leu611Pro) (3/26), c.1349C>A (p.Thr450Lys) (2/26), c.2363C>T (p.Ser788Leu) (2/26), c.2228C>T (p.Pro743Leu) (1/26), c.1525A>G (p.Thr509Ala) (1/26), and c.1349C>T (p.Thr450Met) (1/26). Only 1 heterozygous variation was detected in 2 families. c.2363C>T (p.Ser788Leu), c.1832T>C (p.Leu611Pro) and c.1525A>G (p.Thr509Ala) were not reported previously and predicted as "harmful" to the protein function.@*CONCLUSION@#The main type of ocular albinism is oculocutaneous albinism type II in Liuzhou region, where the most common variations of the P gene were c.803-3C>G and c.1327G>A (p.Val443Ile). Above finding has enriched the variation spectrum of the P gene.

Application of DNA Microarray and Sanger Sequencing to the Genetic Diagnosis of Nonsyndromic Hearing Loss / 听力学及言语疾病杂志

Objective To study genotypes in nonsyndromic hearing loss (NSHL ) patients from Guangxi Zhuang Autonomous Region hearing speech rehabilitation center using DNA microarray in combination with Sanger sequencing .Methods Deaf patients received routine physical and otorhinolaryngoloical examinations as well as pure tone autiometry .Brainstem auditory evoked potential test was performed in uncooperative children .Blood samples were obtained from a total of 136 patients ,male 81 ,female 55 ,age from one year five month to seventeen ,having nonsyndromic hearing loss .Genomic DNA was extracted and then 9 hot mutation spots in 4 susceptibility genes were detected by DNA microarray .GJB2 and SLC26A was further detected by Sanger sequencing in the patients with negative results and heterozygotes .Results Among the 136 patients with nonsyndromic hearing loss ,20 cases were positive for GJB2 gene ,SLC26A4 gene or mitochondrial 12SrRNA gene mutations .There were 14 .71% (20/136)patients were positive for hot mutation spots in the deafness related genes ,25% (34/136)patients carried muta‐tions of deafness related genes using DNA microarray in combination with Sanger sequencing .Six SLC26A4 rare mutations (c .259G> T ,c .754C> T ,c .1229C> T ,c .1548_1549insC ,c .1705+5A>G and c .2086C> T) were de‐tected by Sanger sequencing .c .235delC was the most common mutation in GJB2 gene .c .919-2A>G ,c .754C> T and c .1229C> T were the common mutations in SLC26A4 gene .The mutation rate of GJB2 and SLC26A4 was 38 . 24% .and 58 .82% ,respectively .Conclusion Prevalent deafness-associated gene mutations in the nine loci studied were less frequently detected in nonsyndromic hearing loss patients from Guangxi Zhuang Autonomous Region hear‐ing speech rehabilitation center .It can improve the detection rate of deafness gene mutations by using gene microar‐ray in combination with Sanger sequencing .GJB2 and SLC26A4 are the common causative genes .