OBJECTIVE: To explore the genetic basis for a patient presenting with renal insufficiency. METHODS: The patient was subjected to whole exome sequencing, and the candidate variant was verified by Sanger sequencing. Transcriptional activity of the PAX2 gene was analyzed by using a PRS4-EGFP reporter plasmid. RESULTS: Genetic testing revealed that the patient has carried a novel de novo heterozygous variant c.418C>T (p.Arg140Trp) of the PAX2 gene. The influence of c.389C>G (p.Pro130Arg), c.478G>A (p.Ala160Thr), c.418C>G (p. Arg140Gly) and c.418C>T (p.Arg140Trp) variants on the transcriptional activity was also evaluated. Functional study has illustrated that the PAX2-P130R, PAX2-R140G and PAX2-R140W variants all had a significant inhibitory effect on the transcriptional activity, but not the PAX2-A160T variant. CONCLUSION The isolated renal hypoplasia of the proband is probably due to the likely pathogenic variant of the PAX2 gene.
Coloboma/genetics* ; Genetic Testing ; Humans ; Mutation ; PAX2 Transcription Factor/genetics* ; Renal Insufficiency/genetics* ; Vesico-Ureteral Reflux

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.
Carbohydrate Metabolism, Inborn Errors/genetics* ; Child ; Coloboma ; Female ; Humans ; Microcephaly/genetics* ; Mutation ; Phenotype ; Phosphoglycerate Dehydrogenase/genetics* ; Psychomotor Disorders/genetics* ; Seizures/genetics* ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with microphthalmia. METHODS: Clinical data of the proband was collected. Whole exome sequencing (WES) was carried out to screen potential pathogenic variants in the proband. Candidate variant was verified by Sanger sequencing of the proband and his family members. Pathogenicity of the variant was predicted by searching the PubMed database and bioinformatic analysis. Sanger sequencing of amniotic fluid sample was carried out for prenatal diagnosis. RESULTS: The proband and his father were found to harbor a heterozygous c.151C>G (p.R51G) variant of the MAB21L2 gene. The same variant was not found in his mother and grandparents. Based on the guidelines of American College of Medical Genetics, the c.151C>G (p.R51G) variant was predicted as likely pathogenic. CONCLUSION The c.151C>G (p.R51G) variant of the MAB21L2 gene probably underlay the microphthalmia in the proband. Above finding has facilitated prenatal diagnosis for this pedigree.
China ; Coloboma ; Eye Proteins ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; Microphthalmos/genetics* ; Mutation ; Osteochondrodysplasias ; Pedigree ; Pregnancy ; Prenatal Diagnosis

CHARGE syndrome, first described by Pagon, was named for its six major clinical features. They are: coloboma of the eye, heart defects, atresia of the choanae, retarded growth and development including CNS anomalies, genital hypoplasia and/or urinary tract anomalies, and ear anomalies and/or hearing loss. We experienced three cases of CHARGE syndrome who displayed ocular coloboma, heart defects, retarded growth and development, and external ear anomalies, and we also review the previously reported literature concerning CHARGE syndrome.
Abnormalities, Multiple*/genetics ; Abnormalities, Multiple*/diagnosis ; Brain/abnormalities* ; Case Report ; Child, Preschool ; Choroid/abnormalities* ; Coloboma/genetics ; Coloboma/diagnosis* ; Ear, External/abnormalities ; Entropion/genetics ; Entropion/diagnosis ; Exotropia/genetics ; Exotropia/diagnosis ; Exotropia/congenital ; Facial Paralysis/genetics ; Facial Paralysis/congenital ; Female ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/diagnosis* ; Human ; Infant ; Karyotyping ; Male ; Mandible/abnormalities* ; Retina/abnormalities* ; Syndrome

The 22q11 region has been implicated in chromosomal rearrangements that result in altered gene dosage, leading to three different congenital malformation syndromes: DiGeorge syndrome, cat-eye syndrome (CES), and der(22) syndrome. Although DiGeorge syndrome is a common genomic disorder on 22q11, CES is quite rare, and there has been no report of Korean CES cases with molecular cytogenetic confirmation. In this study, we present the phenotypic and genetic characteristics of a 3-month-old boy with CES. Clinical findings included micropthalmia, multiple colobomata, and renal and genital anomalies. Cytogenetic analyses showed the presence of a supernumerary marker chromosome, which was identified as a bisatellited and isodicentric chromosome derived from an acrocentric chromosome. The results of array comparative genomic hybridization and fluorescence in situ hybridization studies confirmed the karyotype as 47,XY,+mar.ish idic(22)(q11.1) (D22S43+).arr 22q11.1(15,500,000-15,900,000)x4, resulting in a partial tetrasomy of 22q11.1. To the best of our knowledge, this is the first report in Korea of CES confirmed by cytogenetic and molecular cytogenetic analyses.
Abnormalities, Multiple/genetics ; Aneuploidy ; Chromosome Disorders/diagnosis/genetics ; *Chromosomes, Human, Pair 22/genetics ; Coloboma/genetics ; Craniofacial Abnormalities/genetics ; Genetic Markers ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Karyotyping ; Male ; Phenotype ; *Tetrasomy ; Ultrasonography, Prenatal

OBJECTIVETo map the candidate gene by linkage analysis in a Chinese family with autosomal dominant congenital retinaochoroidal coloboma.

METHODSA detailed clinical examination was performed for all patients in the family. The genomic DNA of all family members was extracted from peripheral blood leukocytes. Linkage analysis and genome-wide linkage screening was conducted using fluorescent detection of 398 microsatellite markers representing all autosomes at an average resolution of approximately 10 cM. Polymerase chain reaction was carried out to amplify all 398 microsatellite markers. The allele sizes were determined on ABI 3130-Avant genetic analyzer according to an internal size standard, and the results were analyzed using Genescan 3.1 and Genotyper 2.0 software.

RESULTSLinkage analysis showed the markers D2S2382-D2S301-D2S2244-D2S163 co-segregated with the disease locus in all affected members. The maximum Lod score was 3.01(D2S2382).

CONCLUSIONThe candidate region of the disease gene in the family was located in 2q34-2q35.

Asian Continental Ancestry Group ; Chromosome Mapping ; Coloboma ; genetics ; DNA Mutational Analysis ; Family ; Female ; Genetic Linkage ; Genotype ; Humans ; Lod Score ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; genetics ; Myopia ; genetics ; Pedigree ; Polymerase Chain Reaction