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1.
Article in Chinese | WPRIM | ID: wpr-888390

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a case of Lamb-Shaffer syndrome.@*METHODS@#Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing(WES). Suspected variant was verified by Sanger sequencing.@*RESULTS@#The patients was found to harbor a heterozygous c.1495delA(p.Thr499Glnfs*5) frameshift variant of the SOX5 gene by WES. Sanger sequencing confirmed that the same variant was a de novo variant. Based on the American College of Medical Genetics and Genomics guidelines, c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene was predicted to be pathogenic (PVS1+PS2+PM2).@*CONCLUSION@#The c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene probably underlies the Lamb-Shaffer syndrome in this patient.


Subject(s)
Animals , Genomics , Heterozygote , Humans , Mutation , SOXD Transcription Factors/genetics , Sheep , Whole Exome Sequencing
2.
Article in Chinese | WPRIM | ID: wpr-888386

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a Chinese patient featuring cleidocranial dysplasia(CCD).@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the patient and his parents. Whole exome sequencing (WES) was carried out for the patient, and suspected variant was verified by Sanger sequencing.@*RESULTS@#WES has identified a missense c.460G>T (p.Val154Phe) (GRCh37/hg19) variant of the RUNX2 gene. The variant was located in the Runt domain, a highly conserved region (PM1); it was not present in either the Genome Aggregation Database or the 1000 Genomes Project (PM2), and was predicted to have a deleterious effect on the gene product by multiple in silico prediction tools (PP3); the clinical phenotype of the patient was highly consistent with that of cleidocranial dysplasia (PP4). Furthermore, the variant was unreported in medical literature and was absent in both parents (PS2). Based on the American College of Medical Genetics and Genomics guidelines, the c.460 G>T variant of RUNX2 gene was predicted to be pathogenic (PS2+PM1+PM2+PP3+PP4).@*CONCLUSION@#The c.460G>T (p.Val154Phe) variant of the RUNX2 gene probably underlay the clinical phenotype in the patient. Above finding has enabled accurate diagnosis and expanded the spectrum of RUNX2 variants.


Subject(s)
China , Cleidocranial Dysplasia/genetics , Core Binding Factor Alpha 1 Subunit/genetics , Humans , Mutation , Whole Exome Sequencing
3.
Article in Chinese | WPRIM | ID: wpr-888382

ABSTRACT

OBJECTIVE@#To identify the pathogenesis in two patients of restrictive cardiomyopathy (RCM) using high-throughput sequencing.@*METHODS@#Peripheral blood samples from the two patients and their parents were collected and genomic DNAs were extracted to conduct targeted next generation sequencing or whole exome sequencing. Bioinformation analysis was performed to identify the pathogenic variants in genes associated with cardiomyopathy, which were further validated by Sanger sequencing.@*RESULTS@#By high throughput sequencing, we detected a de novo heterozygous variant c.549+1G>T in TNNI3 gene in patient 1. The variant has not been reported previously and was predicted to be pathogenic in line with American College of Medical Genetics and Genomics (ACMG) guidelines (PVS1+PS2+PM2). Another heterozygous variant c.433C>T (p.Arg145Trp) in TNNI3 gene was identified in patient 2 and his father. The variant had been reported as pathogenic variant in Clinvar and HGMD databases; based on ACMG guidelines, the variant was predicted to be likely pathogenic (PS3+PM1+PP3).@*CONCLUSION@#TNNI3 variants may be the causative gene responsible for restrictive cardiomyopathy in the two patients. High throughput sequencing results provide bases for the diagnosis of restrictive cardiomyopathy.


Subject(s)
Cardiomyopathy, Restrictive/genetics , Child , Genomics , Heterozygote , Humans , Mutation , Whole Exome Sequencing
4.
Article in Chinese | WPRIM | ID: wpr-888379

ABSTRACT

OBJECTIVE@#To analyze a pathogenic variant of MEFV gene in a family with autosomal dominant-familial Mediterranean fever (AD-FMF).@*METHODS@#A 5-year-old boy presented with recurrent aseptic meningitis and his major symptoms included recurrent fever with headache and vomiting. His family members including his mother, sister and brother also had recurrent fever. A genetic disease was considered. DNAs were extracted from patient and all his family members' blood samples. Whole exome sequencing was performed to identify putative pathogenic variants that can explain this family's condition and Sanger sequencing was conducted. The impact of detected variants were predicted and validated by bioinformatics.@*RESULTS@#A missense variant c.2229C>G (p.Phe743Leu) in MEFV gene was identified in the proband and his family members including his mother, sister and brother. This variant had not been reported in China previously, but the locus of it had already been reported in Arabic patient with AD-FMF (PS1). This variant was absent in major allele frequency databases (PM2) and had been predicted to be pathogenic based on Mutationtaster, PROVEAN and PolyPhen-2. In addition, the change of amino acid, locating in 743 locus of pyrin protein, encoding by MEFV gene, was found to cause SPRY_PRY_TRIM20 and SPRY_superfamily domain destroyed and finally influenced the fuction of pyrin protein. On the other hand, using UCSF chimera software, we find the variant c.2229C>G (p.Phe743Leu) can induce serious influence to the spatial structure of pyrin protein and loss of protein fuction (PP3). According to the ACMG variant classification guideline, the variant c.2229C>G (p.Phe743Leu) in MEFV gene was classified as likely pathogenic (PS1+PM2+PP3).@*CONCLUSION@#The condition of this AD-FMF family may be attributed to the missense variant c.2229C>G (p.Phe743Leu) in MEFV gene. The recurrent aseptic meningitis was a very rare manifestation in AD-FMF patients and had not been reported in China previously. The clinical and genetic findings of the present study are helpful for the further understanding of AD-FMF.


Subject(s)
Child, Preschool , Familial Mediterranean Fever/genetics , Gene Frequency , Genetic Testing , Humans , Male , Mutation , Pyrin/genetics , Whole Exome Sequencing
5.
Article in Chinese | WPRIM | ID: wpr-888376

ABSTRACT

OBJECTIVE@#To explore the clinical features and genetic basis for a patient diagnosed with creatine deficiency syndrome (CDS).@*METHODS@#The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. The level of creatine was determined by using a magnetic resonance spectrum (MRS) method.@*RESULTS@#The patient presented with development delay and poor response to stimuli. No obvious abnormality was found with his muscle tone and strength of his limbs. Borderline EEG was detected. MRI showed abnormal development of the white matter and dysplasia of corpus callosum. Urine organic acid screening has shown increased glycerin-3-phosphate. WES revealed that the patient has carried compound heterozygous variants of the GAMT gene, namely c.412C>T and IVS4-1G>A, which were respectively derived from his mother and father. MRS showed reduced creatine in bilateral basal ganglia. Functional study of the splicing site suggested that the IVS4-1G>A variant has resulted skipping of exon 5 upon splicing.@*CONCLUSION@#The compound variants of the GAMT gene probably underlay the disease in this child. Above finding has enriched the spectrum of GAMT gene variants.


Subject(s)
Child , Creatine , Exons , Humans , Mutation , Syndrome , Whole Exome Sequencing
6.
Article in Chinese | WPRIM | ID: wpr-888371

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a fetus with cerebellar dysplasia and widened lateral ventricles.@*METHODS@#The couple have elected induced abortion after careful counseling. Skin tissue sample from the abortus and peripheral venous blood samples from both parents were collected for the extraction of genomic DNA, which was then subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing.@*RESULTS@#Prenatal ultrasonography showed increased nuchal translucency (0.4 cm) and widened lateral ventricles. Magnetic resonance imaging revealed infratentorial brain dysplasia. By DNA sequencing, the fetus was found to carry compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene, which were inherited from its father and mother, respectively. Among these, c.1A>G was known to be pathogenic, but the pathogenicity of c.1564G>A was unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.1564G>A variant of RARS2 gene was predicted to be likely pathogenic(PM2+PM3+PP3+PP4).@*CONCLUSION@#The compound heterozygous variants c.1A>G and c.1564G>A of RARS2 gene contributed to the fetus suffering from pontocerebellar hypoplasia type 6, which expanded variant spectrum of RARS2 gene.


Subject(s)
Female , Fetus , Genomics , Humans , Mutation , Olivopontocerebellar Atrophies , Pregnancy , Whole Exome Sequencing
7.
Article in Chinese | WPRIM | ID: wpr-888368

ABSTRACT

OBJECTIVE@#To explore the genetic basis of a child with holoprosencephaly.@*METHODS@#Genomic DNA of the child was extracted and subjected to whole exome sequencing. Suspected variant was verified by Sanger sequencing of her family members.@*RESULTS@#Cranial MRI suggested lobulated holoprosencephaly with partial absence of corpus callosum. Genetic testing revealed that she has carried a heterozygous c.517C>G (p.His173Asp) variant of the SIX3 gene, for which both of her parents were of wild type. Based on the American College of Medical Genetics and Genomics guidelines, the c.517C>G variant of SIX3 gene was predicted to be pathogenic (PS2+PM1+PM2+PM5+PP3).@*CONCLUSION@#The SIX3 gene c.517C>G variant probably underlay the multiple malformations in this child. Above finding has enabled her definite diagnosis.


Subject(s)
Child , Family , Female , Heterozygote , Holoprosencephaly/genetics , Humans , Mutation , Whole Exome Sequencing
8.
Article in Chinese | WPRIM | ID: wpr-888363

ABSTRACT

OBJECTIVE@#To explore the genetic basis of four children with congenital hyperinsulinemia (CHI).@*METHODS@#The four children were subjected to high-throughput whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing.@*RESULTS@#WES analysis has identified 4 variants in the ABCC8 gene and 1 variant in GLUD1, including a ABCC8 c.382G>A variant in case 1, compound heterozygous c.698T>C and c.4213G>A variants of the ABCC8 gene concomitant with a de novo 14.9 Mb microduplication of chromosome 15 in case 2, and ABCC8 c.331G>A variant in case 3, and de novo c.955T>C variant of the GLUD1 gene in case 4. Of these, c.698T>C of the ABCC8 gene and c.955T>C of the GLUD1 gene were unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.382G>A(p.Glu128Lys), c.698T>C(p.Met233Thr) and c.4213G>A(p.Asp1405Asn) variants of ABCC8 gene and c.955T>C(p.Tyr319His) variant of GLUD1 gene were predicted to be likely pathogenic(PM1+PM2+PP3+PP4, PM1+PM2+PM5+PP3+PP4, PM1+PM2+PP3+PP4 and PS1+PM1+PM2+PP3), and the c.331G>A (p.Gly111Arg) variant of ABCC8 gene was predicted to be uncertain significance(PM1+PM2+PP4).@*CONCLUSION@#The variants of the ABCC8 and GLUD1 genes probably underlay the pathogenesis of CHI in the four patients. Above results have facilitated clinical diagnosis and genetic counseling for the affected families.


Subject(s)
Child , Genomics , High-Throughput Nucleotide Sequencing , Humans , Hyperinsulinism , Mutation , Whole Exome Sequencing
9.
Article in Chinese | WPRIM | ID: wpr-888360

ABSTRACT

OBJECTIVE@#To analyze the pathogenic variants of the KIF1A gene and its corresponding protein structure in an autism spectrum disorder (ASD) family trio carrying harmful missense variants in the KIF1A gene.@*METHODS@#The peripheral blood DNA of the patient and his parents was extracted and sequenced using whole exome sequencing (WES) technology and verified by Sanger sequencing. Bioinformatics software SIFT, PolyPhen-2, Mutation Taster, and CADD software were used to analyze the harmfulness and conservation of variants. The Human Brain Transcriptome (HBT) database was used to analyze the expression of the KIF1A gene in the brain. PredictProtein and SWISS-MODEL were further used to predict the secondary structure and tertiary structure of KIF1A wild-type protein and variant protein. PyMOL V2.4 was utilized to investigate the change of hydrogen bond connection after protein variant.@*RESULTS@#The WES sequencing revealed a missense variant c.664A>C (p.Asn222His) in the child's KIF1A gene, and this variant was a de novo variant. The harmfulness prediction results suggest that this variant is harmful. By analyzing expression level of KIF1A gene in the brain. It is found that KIF1A gene widely expressed in various brain regions during embryonic development. By analyzing the variant protein structure, the missense variant of KIF1A will cause many changes in the secondary structure of protein, such as alpha-helix, beta-strand, and protein binding domain. The connection of hydrogen bond and spatial structure will also change, thereby changing the original biological function.@*CONCLUSION@#The KIF1A gene may be a risk gene for ASD.


Subject(s)
Autism Spectrum Disorder/genetics , Child , Female , Humans , Kinesin/genetics , Mutation , Mutation, Missense , Pregnancy , Protein Domains , Whole Exome Sequencing
10.
Article in Chinese | WPRIM | ID: wpr-879851

ABSTRACT

This is a case report on a 1-day-old male neonate admitted due to a weak cry for 1 day and recurrent circumoral cyanosis for 2 hours. He had unusual facial features at birth, with a single transverse palmar crease on both hands, flat feet, weak cry, feeding difficulties, congenital heart disease, and abnormality on cerebral MRI. Whole exome sequencing showed a


Subject(s)
Exons , Genetic Testing , Humans , Infant, Newborn , Intellectual Disability/genetics , Male , Mutation , Whole Exome Sequencing
11.
Article in Chinese | WPRIM | ID: wpr-879632

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a fetus with renal abnormalities through whole exome sequencing and imaging examination.@*METHODS@#Clinical data and result of medical imaging of the fetus was collected. Amniotic fluid sample was collected for the extraction of fetal DNA. Whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing.@*RESULTS@#Prenatal ultrasonography showed that the fetus had bilateral enlargement of the kidneys with hyperechogenicity and diffuse renal cysts. Whole exome sequencing revealed that the fetus carried compound heterozygous variants of the PKHD1 gene, namely c.5137G>T and c.2335_2336delCA, which were derived from its mother and father, respectively.@*CONCLUSION@#The fetus was diagnosed with autosomal recessive polycystic kidney disease through combined prenatal ultrasonography and whole exome sequencing. The compound heterozygous variants of the PKHD1 gene probably underlay the pathogenesis in the fetus. The results have enabled prenatal diagnosis and genetic counseling for its parents.


Subject(s)
Female , Genetic Testing , Humans , Polycystic Kidney, Autosomal Recessive/genetics , Pregnancy , Prenatal Diagnosis , Receptors, Cell Surface/genetics , Whole Exome Sequencing
12.
Article in Chinese | WPRIM | ID: wpr-879627

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child featuring global developmental delay.@*METHODS@#DNA was extracted from peripheral blood sample taken from the patient and subjected to whole exome sequencing. Suspected variants were verified by Sanger sequencing of his family members.@*RESULTS@#A heterozygous c.239T>C (p.Ile80Thr) variant of the GNB1 gene was detected in the proband, which was a verified to be de novo in origin.@*CONCLUSION@#The heterozygous c.239T>C (p.Ile80Thr) variant of the GNB1 gene probably underlay the disease in this child.


Subject(s)
Arthrogryposis , Child , Family , GTP-Binding Protein beta Subunits , Heterozygote , Humans , Intellectual Disability/genetics , Whole Exome Sequencing
13.
Article in Chinese | WPRIM | ID: wpr-879608

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a girl featuring bone and tooth mineralization disorder, premature deciduous teeth, rickets and short stature.@*METHODS@#Genomic DNA was extracted and subjected to high-throughput whole exome sequencing. Suspected variants were confirmed by Sanger sequencing. Impact of potential variants was analyzed with bioinformatic software.@*RESULTS@#The child was found to carry compound heterozygous missense variants of the ALPL gene, including c.1130C>T (p.A377V), a known pathogenic mutation inherited from her father, and c.1300G>A (p.V434M) inherited from her mother, which was unreported previously and predicted to be likely pathogenic based on standards and guidelines from the American College of Medical Genetics and Genomics (PM2+PM5+PP3+PP4).@*CONCLUSION@#The compound heterozygous variants of c.1130C>T (p.Ala377Val) and c.1300G>A (p.Val434Met) of the ALPL gene probably underlay the disease in this child. Above finding has enriched the spectrum of ALPL gene variants.


Subject(s)
Alkaline Phosphatase , Child , Female , Genomics , High-Throughput Nucleotide Sequencing , Humans , Hypophosphatasia/genetics , Mutation , Whole Exome Sequencing
14.
Article in Chinese | WPRIM | ID: wpr-879601

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with non-syndromic hearing loss (NSHL).@*METHODS@#Commercialized gene chip was applied to detect common mutations associated with congenital deafness. Whole exome sequencing was carried out for patients for whom gene chip yielded a negative result. Candidate variants were verified by Sanger sequencing.@*RESULTS@#Two patients from the pedigree were discovered to carry compound heterozygous variants of the TRIOBP gene, namely c.3299C>A and c.5185-2A>G. Their parents had normal hearing and were both heterozygous carriers of the above variants. Both variants had co-segregated with the disease phenotype in the pedigree and were unreported previously.@*CONCLUSION@#Pathogenic variants of the TRIOBP gene comprise an important factor for NSHL. The novel c.5185-2A>G and c.3299C>A variants discovered in this study have enriched the mutational spectrum of the TRIOBP gene and enabled molecular diagnosis and genetic counseling for the family.


Subject(s)
Deafness/genetics , Hearing Loss, Sensorineural/genetics , Heterozygote , Humans , Microfilament Proteins/genetics , Mutation , Pedigree , Whole Exome Sequencing
15.
Article in Chinese | WPRIM | ID: wpr-879586

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a patient featuring Rotor syndrome.@*METHODS@#Clinical data of the patient was collected. Whole exome sequencing (WES) based on high-throughput sequencing technology was carried out. Long-interspersed element-1 (LINE-1) insertion in intron 5 of the SLCO1B3 gene was detected by using tri-primer single tube PCR.@*RESULTS@#WES revealed that the patient has carried homozygous c.1738C>T nonsense variants of the SLCO1B1 gene. He was also found to harbor a homozygous insertion of LINE-1 in intron 5 of the SLCO1B3 gene, which has caused skipping of exon 5 or exons 5 to 7 and introduced a stop codon in the SLCO1B3 transcript.@*CONCLUSION@#The homozygous c.1738C>T variant of the SLCO1B1 gene and homozygous insertion of LINE-1 in intron 5 of the SLCO1B3 gene probably underlay the Rotor syndrome in this patient.


Subject(s)
Exons/genetics , Homozygote , Humans , Hyperbilirubinemia, Hereditary , Introns/genetics , Liver-Specific Organic Anion Transporter 1 , Male , Whole Exome Sequencing
16.
Article in Chinese | WPRIM | ID: wpr-879585

ABSTRACT

OBJECTIVE@#To explore the clinical and genetic characteristics of a child with frontometaphyseal dysplasia 1 (FMD1) due to variant of FLNA gene.@*METHODS@#Clinical phenotype of the patient was analyzed. Whole exome sequencing (WES) was carried out to detect pathogenic genetic variants. Sanger sequencing was used to verify the result in his parents.@*RESULTS@#The 2-year-and-9-month-old boy presented with facial dysmorphism (supraorbital hyperostosis, down-slanting palpebral fissure and ocular hypertelorism), skeletal deformities (bowed lower limbs, right genu valgum, left genu varus, slight deformity of index and middle fingers, and flexion contracture of little fingers). He also had limited left elbow movement. High-throughput sequencing revealed that he has carried a de novo heterogeneous c.3527G>A (p.Gly1176Glu) missense variant of the FLNA gene. The same variant was found in neither parent.@*CONCLUSION@#The clinical manifestations of FMD1 such as joint contracture and bone dysplasia can occur in infancy and deteriorate with age, and require long-term follow-up and treatment. Above finding has expanded the spectrum of FLNA gene variants.


Subject(s)
Child , Filamins/genetics , Forehead/abnormalities , Humans , Infant , Male , Osteochondrodysplasias/genetics , Phenotype , Whole Exome Sequencing
17.
Article in Chinese | WPRIM | ID: wpr-879570

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child affected with Bainbridge-Ropers syndrome.@*METHODS@#Genomic DNA was extracted from peripheral venous blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out to detect genetic variant of the proband. Candidate variant was verified by Sanger sequencing.@*RESULTS@#The 3-year-old boy presented with psychomotor retardation, linguistic difficulties, mental retardation and peculiar craniofacial phenotype. A de novo heterozygous nonsense variant of the ASXL3 gene, c.3106C>T, was identified by WES in the proband, and the same mutation was not found among his parents. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.3106C>T variant was predicted to be pathogenic (PVS1+PS2+PP4).@*CONCLUSION@#The heterozygous variant c.3106C>T of the ASXL3 gene probably underlies the Bainbridge-Ropers syndrome in the patient. Above result has enabled the clinical diagnosis and genetic counseling for the family.


Subject(s)
Child , Child, Preschool , Heterozygote , Humans , Intellectual Disability/genetics , Male , Mutation , Phenotype , Transcription Factors/genetics , Whole Exome Sequencing
18.
Article in Chinese | WPRIM | ID: wpr-879566

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child with mental and motor retardation, language impairment, facial dysmorphism and epilepsy.@*METHODS@#Whole exome sequencing was carried out to detect pathogenic variant in the proband, and candidate variant was selected based on his phenotype. Sanger sequencing was used to verify the variant in the proband, his parents and other family members.@*RESULTS@#The proband was found to carry a frameshifting mutation of MBD5 gene, namely c.2217delT (p.F739Lfs*6), which was inherited from his mother and unreported previously. Sanger sequencing confirmed that his brother carried the same mutation with a similar phenotype. His mother also had poor language expression when she was young, in addition with poor academic performance, though she could do some housework and had no history of convulsion.@*CONCLUSION@#A novel pathogenic variant of the MBD5 gene was discovered, which has enriched the mutational spectrum of the MBD5 gene. Above discovery has enabled genetic counseling and prenatal diagnosis for the family.


Subject(s)
Child , DNA-Binding Proteins/genetics , Female , Humans , Intellectual Disability/genetics , Male , Mutation , Pedigree , Phenotype , Pregnancy , Whole Exome Sequencing
19.
Article in Chinese | WPRIM | ID: wpr-879551

ABSTRACT

OBJECTIVE@#To explore the genetic basis of a pedigree affected with peroneal muscular atrophy.@*METHODS@#Neuroelectrophysiological examination and whole exome sequencing were carried out for the proband, a six-year-and-ten-month-old boy. Suspected variant was verified in his family members through Sanger sequencing. Bioinformatic analysis was carried to predict the conservation of amino acid sequence and impact of the variant on the protein structure and function.@*RESULTS@#Electrophysiological examination showed demyelination and axonal changes of motor and sensory nerve fibers. A heterozygous missense c.1066A>G (p. Thr356Ala) variant was found in exon 11 of the MFN2 gene in the proband and his mother, but not in his sister and father. Bioinformatic analysis using PolyPhen-2 and Mutation Taster software predicted the variant to be pathogenic, and that the sequence of variation site was highly conserved among various species. Based no the American College of Medical Genetics and Genomics standards and guidelines, the c.1066A>G (p. Thr356Ala) variant of MFN2 gene was predicted to be likely pathogenic (PS1+ PM2+ PP3+ PP4).@*CONCLUSION@#The heterozygous missense c.1066A>G (p.Thr356Ala) variant of the MFN2 gene probably underlay the disease in the proband, and the results have enabled genetic counseling and prenatal diagnosis for this family.


Subject(s)
Charcot-Marie-Tooth Disease/genetics , Child , China , Drosophila Proteins/genetics , Exons , Female , Heterozygote , Humans , Male , Membrane Proteins/genetics , Mutation , Pedigree , Pregnancy , Whole Exome Sequencing
20.
Article in Chinese | WPRIM | ID: wpr-879548

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child with ocular anomaly, microcephaly, growth retardation and intrauterine growth restriction.@*METHODS@#The patient underwent ophthalmologic examinations including anterior segment photography, fundus color photography, and fundus fluorescein angiography. The patient and her parents were subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The patient was found to have bilateral persistent pupillary membrane and coloboma of inferior iris, in addition with macular dysplasia and radial pigmentation near the hemal arch of the temporal retina. She was found to have carried compound heterozygous missense variants of the PHGDH gene, namely c.196G>A and c.1177G>A, which were respectively inherited from her father and mother. Bioinformatic analysis suggested both variants to be pathogenic.@*CONCLUSION@#The patient was diagnosed with phosphoglycerate dehydrogenase deficiency. Above finding has enriched the phenotypic spectrum of the disease with ocular manifestations.


Subject(s)
Carbohydrate Metabolism, Inborn Errors/genetics , Child , Coloboma , Female , Humans , Microcephaly/genetics , Mutation , Phenotype , Phosphoglycerate Dehydrogenase/genetics , Psychomotor Disorders/genetics , Seizures/genetics , Whole Exome Sequencing
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