OBJECTIVETo delineate the clinical and genetic characteristics of a girl featuring motor retardation, language retardation and regression, and light persisting diarrhea.

METHODSThe patient was clinically examined and tested by tandem mass spectrometry and next generation sequencing.

RESULTSThe proband could not stand and walk alone, and had light persisting diarrhea. She manifested language development retardation and regression. Laboratory tests were all normal, but the screening of metabolic disorders for urine and blood showed deficiency of short chain coenzyme A dehydrogenase due to elevated ethylmalonic acid and butyryl carnitine. By next generation sequencing, two compound heterozygous mutations of the ETHE1 gene, c.2T>A and c.488G>A, were discovered in the proband, which were respectively inherited from her father and mother. Bioinformatics analysis predicted both mutations to be pathogenic. The patient was diagnosed with ethylmalonic encephalopathy. Vitamin B1, B2, Coenzyme Q10, and L-carnitine were prescribed. The patient deteriorated and required liver transplantation at 4-year-1-month.

CONCLUSIONBased on the clinical and genetic analysis, the proband was diagnosed with ethylmalonic encephalopathy caused by ETHE1 gene mutation. Next generation sequencing has provided a powerful tool for the diagnosis of such disorders.

OBJECTIVETo explore the genetic cause for two children with omphalocele.

METHODSThe patients were examined, and the medical history of their families was collected. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to detect potential mutation in the patients.

RESULTSLoss of methylation of imprinting center 2 (IC2) at the 11p15.5 region of the maternal chromosome was detected in both children.

CONCLUSIONThe two patients were diagnosed with Beckwith-Wiedemann syndrome by MS-MLPA. The loss of methylation of IC2 probably underlies the disease in both patients.

Beckwith-Wiedemann Syndrome ; genetics ; Chromosomes, Human, Pair 11 ; DNA Methylation ; Female ; Genomic Imprinting ; Humans ; Infant ; Infant, Newborn ; Male ; Multiplex Polymerase Chain Reaction

OBJECTIVETo explore the genetic cause of a Chinese boy with unexplained mental retardation, and analyze the pattern of inheritance for his family.

METHODSRoutine karyotyping, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH) were used to detect chromosome abnormalities in the patient and his families.

RESULTSChromosome analysis suggested that the proband and 7 affected individuals had an identical karyotype 46,XN,der(22)t(3;22)(q28;q13)pat, while his father and 5 other relatives carried a same karyotype of 46,XN,t(3;22)(q28;q13). His mother and other family members were normal. CMA analysis confirmed that the patient had a 9.0 Mb duplication at 3q28q29, in addition with a 1.7 Mb deletion at 22q13.3. Above results were confirmed by FISH.

CONCLUSIONThe abnormal phenotypes of the proband and his family members from five generations have conformed to those of 3q duplication and 22q13.3 deletion caused by unbalanced translocation involving chromosomes 3q and 22q. The presence of multiple patients in this family may be attributed to abnormal gametes produced by parental balanced translocations involving 3q and 22q.

Chromosome Deletion ; Chromosome Duplication ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Cytogenetic Analysis ; methods ; Family Health ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Pedigree ; Translocation, Genetic

OBJECTIVE: To validate the diagnosis of an infant with elevated urine 3-methylglutaconic acid (3-MGA) through sequencing of the CLPB gene. METHODS: Genomic DNA of the infant was sequenced by next generation sequencing (NGS), and candidate pathogenic variants were verified by Sanger sequencing and bioinformatics analysis. RESULTS: NGS has revealed that the infant has carried a c.1085G>A (p.Arg362Gln) and a c.1700A>C (p.Tyr567Ser) of the CLPB gene, which were respectively inherited from her parents. Among these, c.1085G>A (p.Arg362Gln) is a novel variant which was unreported previously, and based on the ACMG guidelines, it was predicted to be a possible pathogenic variant. CONCLUSION Compound heterozygous variants c.1085G>A (p.Arg362Gln) and c.1700A>C (p.Tyr567Ser) of the CLPB gene probably underlay the disease in this infant. Genetic testing has confirmed the diagnosis.

OBJECTIVE: To analyze the clinical and genetic characteristics of an infant girl featuring comprehensive developmental backwardness. METHODS: The patient was subjected to clinical examination, gas chromatography mass spectrometry and next-generation sequencing (NGS). RESULTS: The child was insensitive to sound, could not turn over, raise head, laugh or recognize his mother. Laboratory tests were all normal, but metabolic analysis suggested 3-methylglutaconic aciduria due to elevated 3-methylglutaconic acid and 3-methylglutaric acid. NGS has detected two compound heterozygous CLPB variants in the child, namely c.1085G>A and c.1700A>C, which were respectively inherited from her father and mother. Bioinformatic analysis predicted both variants to be pathogenic. The patient was diagnosed with 3-methylglutaconic aciduria type VII (MGCA7). CONCLUSION The MGCA7 in the child was probably caused by CLPB gene variants. NGS has provided a powerful diagnostic tool for this rare disorder.
Endopeptidase Clp ; genetics ; Female ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Metabolism, Inborn Errors ; genetics

This article reported a prenatal diagnosis of fetal bladder prolapse caused by patent urachus and ruptured urachal cyst. On August 8, 2023 (12 weeks and 5 days of gestation), a routine prenatal ultrasound examination in Heping Hospital Affiliated to Changzhi Medical College revealed that one of the twins had an anechoic area (22.0 mm×17.0 mm) protruding into the umbilical cord at the umbilical opening, which was connected to the bladder in a bell-shaped manner through an unclosed urachus. Regular follow-up ultrasounds indicated that the cyst increased in size as the pregnancy progressed, the biggest was 38.3 mm×30.2 mm (23 +5 gestational weeks). At 33 weeks and 5 days of gestation, ultrasound showed that the cyst had disappeared, and a high-echo mass (21.3 mm×15.2 mm) was visible at the umbilical opening, while the bladder was not visible even upon repeated scans. These observations led to the diagnosis of bladder prolapse due to patent urachus and ruptured urachal cyst. Postnatally, the infant was transferred to an external hospital for surgical treatment, where the diagnosis of bladder prolapse was further confirmed and prolapse repair and umbilicoplasty were done. Postoperative pathology verified that the protruding high-echo mass was bladder tissue. Follow-up examinations at 2 months of age showed no significant complications.