scholarly journals Molecular diagnosis of Phenylketonuria in 157 Families and Prenatal Diagnosis of Phenylketonuria

2019 ◽  
Author(s):  
Yang Xiao ◽  
Qiang Gu ◽  
Hairong Wu ◽  
Songtao Wang ◽  
Pei Pei ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Mutant Allele ◽  
North China ◽  
Novel Mutation ◽  
Pathogenic Mutation ◽  
Large Deletions ◽  
Flanking Sequences ◽  
Duplication Detection ◽  
Pah Gene ◽  
Genetic Metabolic Disease

Abstract Background Phenylketonuria (PKU) is a genetic metabolic disease with a relatively higher incidence, but only a few studies about the prenatal diagnosis of PKU have been reported so far in China. The aim of this study was to characterize the spectrum of mutations in PAH gene in PKU probands and the prenatal diagnosis of PKU in north China.Methods A total of 157 families in which PKU patients had been diagnosed were included in the study. The 13 exons and their flanking sequences of PAH gene were amplified by PCR and sequenced in the probands. If none or only one mutant allele was found in the probands, the sample was subjected to MLPA for large deletions/duplication detection in PAH gene. Prenatal diagnosis was performed for pregnant women in these families.Results Pathogenic mutation in PAH was found in 2 alleles in 148 probands and in one allele in 7 probands, and the mutation was not detected in 2 probands. There were 289 point mutants, 10 frame-shift mutations and 4 large deletions with a total of 80 kinds of mutations. The most prevalent mutations were R243Q (17.2%), EX6-96A>G (8.6%) and V399V (8.0%). We also found a novel mutation of 163_164insATAT. Prenatal diagnosis of 95 families found 21 healthy fetus (20.4%), 52 carriers (50.5%) and 30 patients (29.1%), and the accuracy of prenatal diagnosis was confirmed after birth of the fetuses.Conclusion We present here a spectrum of mutations in PAH gene in PKU patients in north China. Prenatal diagnosis for PKU is useful for PKU families to prevent birth of another PKU case.

A Chinese family with familial hemiplegic migraine type 2 due to a novel missense mutation in ATP1A2

Cephalalgia ◽  
2019 ◽  
Vol 39 (11) ◽  
pp. 1382-1395
Author(s):  
Wenjing Tang ◽  
Meichen Zhang ◽  
Enchao Qiu ◽  
Shanshan Kong ◽  
Yingji Li ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Pathogenic Mutation ◽  
Familial Hemiplegic Migraine ◽  
Chinese Family ◽  
Hemiplegic Migraine ◽  
Pathogenic Potential ◽  
The Family

Background ATP1A2 has been identified as the genetic cause of familial hemiplegic migraine type 2. Over 80 ATP1A2 mutations have been reported, but no data from Chinese family studies has been included. Here, we report the first familial hemiplegic migraine type 2 Chinese family with a novel missense mutation. Methods Clinical manifestations in the family were recorded. Blood samples from patients and the unaffected members were collected for whole-exome sequencing to identify the pathogenic mutation. Seven online softwares (SIFT, PolyPhen-2, PROVEAN, PANTHER, MutationTaster2, MutationAssessor and PMut) were used for predicting the pathogenic potential of the mutation. PredictProtein, Jpred 4 and PyMOL were used to analyze structural changes of the protein. The mutation function was further tested by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Results All patients in the family had typical hemiplegic migraine attacks. Co-segregation of the mutation with the migraine phenotype in four generations, with 10 patients, was completed. The identified novel mutation, G762S in ATP1A2, exhibited the disease-causing feature by all the predictive softwares. The mutation impaired the local structure of the protein and decreased cell viability. Conclusion G762S in ATP1A2 is a novel pathogenic mutation identified in a Chinese family with familial hemiplegic migraine, which causes loss of function by changing the protein structure of the Na+/K+-ATPase α2 subunit.

scholarly journals Prenatal diagnosis using genetic sequencing and identification of a novel mutation in MMACHC

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Yanan Zong ◽  
Ning Liu ◽  
Zhenhua Zhao ◽  
Xiangdong Kong
Keyword(s):  
Prenatal Diagnosis ◽  
Novel Mutation ◽  
Genetic Sequencing

Prenatal diagnosis of a novel mutation, c.529C>T (p.Q177X), in the BCKDHA gene in a family with maple syrup urine disease

2009 ◽  
Vol 32 (S1) ◽  
pp. 33-36 ◽  
Author(s):  
R. Tammachote ◽  
S. Tongkobpetch ◽  
T. Desudchit ◽  
K. Suphapeetiporn ◽  
V. Shotelersuk
Keyword(s):  
Prenatal Diagnosis ◽  
Maple Syrup Urine Disease ◽  
Novel Mutation ◽  
Maple Syrup ◽  
Urine Disease

Prenatal diagnosis of Sanfilippo type A syndrome in a family with S66W mutant allele

1999 ◽  
Vol 19 (10) ◽  
pp. 993-994 ◽  
Author(s):  
Paola Di Natale ◽  
Guglielmo R. D. Villani ◽  
Sabrina Esposito ◽  
Nicola Balzano ◽  
Mirella Filocamo ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Mutant Allele ◽  
Type A

scholarly journals A Novel Variant of the SH2B1 Gene in an Obese Child With Type 2 Diabetes

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A32-A32
Author(s):  
Mariaester Makacio Morillo ◽  
Supamit Ukarapong ◽  
Tossaporn Seeherunvong
Keyword(s):  
Type 2 Diabetes ◽  
Behavioral Problems ◽  
Novel Mutation ◽  
Fasting Blood Glucose ◽  
Pathogenic Mutation ◽  
The United States ◽  
Maladaptive Behavior ◽  
Leptin Resistance ◽  
Protein Functions

Abstract Obesity in children and adolescents is at epidemic levels in the United States and creates high risk for comorbidities later in life. Childhood obesity is thought to be the result of behavioral and nutritional problems. Although genetic factors may play a role in the etiology of obesity, monogenic forms of obesity are rare. We present a child with obesity, behavioral problems, leptin resistance, and type 2 diabetes who also carries a mutation of Sarcoma Homologous 2B adapter protein 1 (SH2B1). The subject was evaluated at 13 7/12 years old. He had polyphagia, learning disability, aggressive behavior and marked obesity. At ages 9,11, and 13 years respectively, his BMI was 9%, 16%, and 52% above the 95th percentile. At 13 7/12 years old, his height was at the 80th percentile and BMI was 66% above the 95th percentile. He had marked acanthosis nigricans and he was prepubertal. Fasting blood glucose and insulin levels were 116 mg/dl and 592 mIU/L, respectively. Hemoglobin A1c was 6.5% and metformin therapy was initiated for type 2 diabetes. Fasting leptin level (41.5 ng/mL) was markedly elevated indicating leptin resistance. DNA methylation study excluded Prader-Willi syndrome. DNA sequencing indicated a novel heterozygous c.1555G>T variant of SH2B1 gene, which is predicted to result in the amino acid substitution p. Asp519Tyr. The analysis by PolyPhen-2 and MutationTaster predicts that the variant is a pathogenic mutation affecting protein functions. SH2B1 interacts with JAK2 and may play a role in insulin signaling. Pathogenic heterozygous variants in SH2B1 have been associated with obesity, insulin resistance and maladaptive behavior phenotypes (Pearce et al, 2014). Sh2b1-null mice develop severe leptin resistance, obesity, and type 2 diabetes. Our report underscores the importance of investigating monogenic causes of obesity in subjects who present severe obesity, diabetes, and behavioral problems. Additional studies are needed to determine the association between this novel mutation and the clinical features of this patient.

scholarly journals Prevalence of Mutations in the GJB2, SLC26A4, GJB3, and MT-RNR1 Genes in 103 Children with Sensorineural Hearing Loss in Shaoxing, China

2018 ◽  
Vol 97 (6) ◽  
pp. E33-E38 ◽  
Author(s):  
Hong Yu ◽  
Dan Liu ◽  
Jingqun Yang ◽  
Zhiqiang Wu
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Genetic Screening ◽  
Mutant Allele ◽  
Hot Spot ◽  
Pathogenic Mutation ◽  
Sensorineural Hearing ◽  
Common Cause ◽  
Vestibular Aqueduct ◽  
Multiple Pcr

Mutations in the GJB2, SLC26A4, GJB3, and MT-RNR1 genes are known to be a common cause of hearing loss. However, the frequency of hot-spot mutations and genotype-phenotype correlations in patients with sensorineural hearing loss (SNHL) has been less frequently reported. We conducted a study of 103 children—56 boys and 47 girls, aged 5 months to 9 years (mean: 4.1 yr)—with SNHL who underwent genetic screening for 20 hot-spot mutations of the GJB2, SLC26A4, GJB3, and MT-RNR1 genes. Mutations were detected by multiple-PCR-based MALDI-TOF MS assay. At least one mutated allele was detected in 48 patients (46.6%), and 30 patients (29.1%) carried pathogenic mutations. Among all the detected mutations, the most common were GJB2 c.235delC and SLC26A4 c.919-2A>G, with allele frequencies of 23.8 and 6.8%, respectively. At least one mutant allele of SLC26A4 was detected in the 13 patients who had an enlarged vestibular aqueduct (EVA). Almost half of the children with SNHL carried a common deafness-related mutation, and nearly one-third carried a pathogenic mutation. The mutations in SLC26A4 were prevalent and correlated strongly with EVA.

A Novel Mutation in Aicardi–Goutières' Syndrome: A Case Report

2020 ◽  
Author(s):  
Motahareh Sheikh-Hosseini ◽  
Mohammad Moarefzadeh ◽  
Hamideh Alavi-Moghaddam ◽  
Saeid Morovvati
Keyword(s):  
Neonatal Jaundice ◽  
Clinical Phenotype ◽  
Novel Mutation ◽  
Genetic Disorder ◽  
Cerebral Atrophy ◽  
Pathogenic Mutation ◽  
Consanguineous Marriage ◽  
The Other ◽  
Congenital Infections ◽  
History Of

AbstractAicardi–Goutières' syndrome (AGS) is a rare heterogeneous genetic disorder characterized by encephalopathy and may bear resemblance to congenital infections. The prevalence of AGS is estimated at more than 4,000 worldwide. Mutations in TREX1 gene are present in ∼22% of patients. We present the case of a 2-year-old boy who came to the Biogene laboratory (Tehran, Iran) with a constellation of congenital disorders but no clear diagnosis. His clinical phenotype consisted of neonatal jaundice, relative microcephaly with diffuse cerebral atrophy in both hemispheres, developmental delay, hypotonia, and nystagmus. There was history of parental consanguineous marriage and prematurity. In our study, a homozygous potentially pathogenic mutation in TREX1 gene associated with AGS1 was detected. This mutation has not been reported in the other patients with AGS. A novel frameshift homozygous potentially pathogenic mutation in TREX1 is postulated to be the cause of disease in our patient.

scholarly journals Auditory Neuropathy Spectrum Disorder due to Two Novel Compound Heterozygous OTOF Mutations in Two Chinese Families

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Yue Qiu ◽  
Sen Chen ◽  
Le Xie ◽  
Kai Xu ◽  
Yi Lin ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Pathogenic Mutation ◽  
Auditory Neuropathy ◽  
Spectrum Disorder ◽  
Compound Heterozygous ◽  
Unique Type ◽  
Chinese Families ◽  
Auditory Neuropathy Spectrum Disorder ◽  
Mutation Database ◽  
Next Generation Sequencing Ngs

Auditory neuropathy spectrum disorder (ANSD), also called auditory neuropathy (AN), is a unique type of prelingual hearing impairment. Up to 10% of deaf infants and children are affected by this disease. Mutation of the OTOF gene which encodes otoferlin is the common cause of congenital nonsyndromic ANSD. To date, over 110 mutations have been identified in the OTOF gene according to the Human Gene Mutation Database (HGMD). Here, next-generation sequencing (NGS) revealed that the compound heterozygous mutations c.4748G>A/c.2523+1G>T and c.5248G>C/c.5098G>C of the OTOF gene were present in two Chinese ANSD patients. Each patient had a known pathogenic mutation (c.4748G>A or c.5098G>C) and a novel mutation (c.2523+1G>T or c.5248G>C). Comparative amino acid sequence analysis across different species revealed that the residues at these novel mutation sites are evolutionarily highly conservative. This indicated that the novel mutations were possible causes of the disorder in the patients. Our findings extend the OTOF mutation spectrum and further confirm the role of the OTOF gene in ANSD.

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