OBJECTIVE: To explore the clinical features and genetic etiology of a child with Wiedemann-Steiner syndrome. METHODS: A child with WSS who was admitted to the Hematology Department of Tianjin Children's Hospital in May 2021 was selected as the subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. The child was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing of the child and his parents. RESULTS: The main clinical features of the child have included pancytopenia, growth and mental retardation, and facial dysmorphism. Whole exome sequencing revealed that the child has harbored a heterozygous variant of the KMT2A gene, namely c.7804delA (p.M2602Cfs*39). Sanger sequencing verified the variant to be de novo in origin. The variant was unreported previously and predicted to be pathogenic based on the guidelines of American College of Medical Genetics and Genomics (PVS1+PS2+PM2). CONCLUSION The heterozygous c.7804delA (p.M2602Cfs*39) variant of the KMT2A gene probably underlay the WSS in this child. Above finding has enriched the mutational spectrum and clinical phenotypes of the KMT2A gene.
Humans ; Abnormalities, Multiple/genetics* ; Intellectual Disability/genetics* ; Mutation ; Syndrome

Abnormalities, Multiple/genetics* ; Costello Syndrome ; Humans ; Whole Genome Sequencing

Myotonic dystrophy type 1 (DM1, OMIM 160900) is a rare autosomal dominant hereditary disease. A case of DM1 patient with early onset diabetes and decreased muscle strength was treated in the Department of Endocrinology, Third Xiangya Hospital, Central South University. The peripheral blood of the patient was collected to extract DNA for gene detection. It was found that the triple nucleotide CTG repeat in the 3'-untranslated region (3'-UTR) of the dystrophia myotonica protein kinase (DMPK) gene was more than 100 times, and the diagnosis of DM1 was clear. For diabetes patients with multiple system abnormalities such as muscle symptoms, attention should be paid to the screening of DM1, a rare disease.
Humans ; Myotonic Dystrophy/genetics* ; Abnormalities, Multiple ; Hospitals ; Universities ; Diabetes Mellitus

OBJECTIVE: To explore the pathogenesis of two siblings (including a fetus) from a pedigree affected with Joubert syndrome. METHODS: Peripheral blood samples of the proband and his parents as well as amniotic fluid and abortion tissues of the fetus were collected. Part of the samples were used for the extraction of DNA, and whole exome sequencing (WES) was carried out to screen potential variants in the proband and his parents. Suspected variants were subjected to bioinformatics analysis with consideration of the clinical phenotype, and were verified by Sanger sequencing of the proband, fetus and their parents.The remainders were used for the extraction of RNA, and the mechanism of splicing variant was validated by reverse transcription-PCR (RT-PCR). RESULTS: WES showed that both patients have carried c.175C>T (p.R59X) and c.553+1G>A compound heterozygous variants of the TMEM237 gene. Among these, c.175C>T was a nonsense mutation inherited from the asymptomatic mother, while c.553+1G>A was an alternative splicing mutation inherited from the asymptomatic father. RT-PCR showed that this variant has resulted in aberrant splicing by exon skipping. CONCLUSION The compound heterozygous variants of the TMEM237 gene probably underlay the etiology of Joubert syndrome in this pedigree. Above finding has enriched the phenotype and variant spectrum of the TMEM237 gene, and facilitated genetic counseling and prenatal diagnosis for the family.
Abnormalities, Multiple/genetics* ; Cerebellum/abnormalities* ; Eye Abnormalities ; Female ; Genotype ; Humans ; Kidney Diseases, Cystic ; Mutation ; Pedigree ; Phenotype ; Pregnancy ; Retina/abnormalities*

OBJECTIVE: To analyze the phenotype and genetic variant of a fetus with dysplasia of cerebellar vermis. METHODS: Gestational status and family history of the gravida was taken in combination with the imaging results of the fetus. Following elected abortion, fetal tissue and peripheral blood samples of the couple were collected for the extraction of genome DNA. Whole exome sequencing was carried out to screen potential variant associated with the phenotype of the proband. Specific PCR primers were designed to verify the results by Sanger sequencing. RESULTS: Prenatal ultrasound revealed that the fetal vermis cerebellum was poorly developed, which was similar to the previous pregnancy. Whole exome sequencing revealed that the fetus has carried compound heterozygous variants of the CPLANE1 gene, namely c.7978C>T and c.7169delT, which were respectively inherited from the husband and wife. CONCLUSION The c.7978C>T and c.7169delT compound heterozygous variants of the CPLANE1 gene probably underlay the dysplasia of cerebellar vermis in the fetus, which has provided a basis for genetic counseling and prenatal diagnosis.
Abnormalities, Multiple/genetics* ; Cerebellum/diagnostic imaging* ; Eye Abnormalities/genetics* ; Female ; Fetus ; Humans ; Kidney Diseases, Cystic ; Mutation ; Phenotype ; Pregnancy ; Retina/abnormalities*

OBJECTIVE: To explore the pathogenesis of two fetuses from one family affected with Joubert syndrome (JS). METHODS: Whole exome sequencing was employed to screen potential mutations in both fetuses. Suspected mutations were verified by Sanger sequencing. Impact of intronic mutations on DNA transcription was validated by cDNA analysis. RESULTS: Two novel TCTN1 mutations, c.342-8A>G and c.1494+1G>A, were identified in exons 2 and 12, respectively.cDNA analysis confirmed the pathogenic nature of both mutations with interference of normal splicing resulting in production of truncated proteins. CONCLUSION The genetic etiology of the family affected with JS has been identified.Above findings have enriched the mutation spectrum of TCTN1gene and facilitated understanding of the genotype-phenotype correlation of JS.
Abnormalities, Multiple ; diagnosis ; genetics ; Cerebellum ; abnormalities ; Eye Abnormalities ; diagnosis ; genetics ; Humans ; Kidney Diseases, Cystic ; diagnosis ; genetics ; Membrane Proteins ; genetics ; Mutation ; Pedigree ; Retina ; abnormalities ; Whole Exome Sequencing

Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome is a rare X-linked dominant and male-lethal multi-system disorder characterized by congenital hemidysplasia, strictly lateralized ichthyosiform nevus and ipsilateral limb defects. CHILD syndrome is caused by mutations of nicotinamide adenine dinucleotide phosphate steroid dehydrogenase-like protein (NSDHL) gene mapped to chromosome Xq28. The gene encodes 3β-hydroxylsterol dehydrogenase, which catalyses a step in the cholesterol biosynthetic pathway. This paper has provided a review for recent progress in research on CHILD syndrome including its clinical aspects, pathology, etiology, pathogenesis, differential diagnosis, and treatment, with a particular emphasis on its treatment..
Abnormalities, Multiple ; genetics ; Genetic Diseases, X-Linked ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Nevus ; genetics ; Syndrome

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with multiple pterygium syndrome (MPS). METHODS: A child with MPS who was treated at the Orthopedics Department of Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University on August 19, 2020 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were also collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing of her parents and bioinformatic analysis. RESULTS: The child, an 11-year-old female, had a complain of "scoliosis found 8 years before and aggravated with unequal shoulder height for 1 year". WES results revealed that she has carried a homozygous c.55+1G>C splice variant of the CHRNG gene, for which both of her parents were heterozygous carriers. By bioinformatic analysis, the c.55+1G>C variant has not been recorded by the CNKI, Wanfang data knowledge service platform and HGMG databases. Analysis with Multain online software suggested that the amino acid encoded by this site is highly conserved among various species. As predicted with the CRYP-SKIP online software, the probability of activation and skipping of the potential splice site in exon 1 caused by this variant is 0.30 and 0.70, respectively. The child was diagnosed with MPS. CONCLUSION The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient.
Humans ; Child ; Female ; Abnormalities, Multiple/genetics* ; Malignant Hyperthermia/genetics* ; Skin Abnormalities/genetics* ; Heterozygote ; Mutation ; Receptors, Nicotinic/genetics*

OBJECTIVE: To explore the genetic basis for two unrelated patients with global developmental delay and coarse facial features. METHODS: Clinical data and family history of the two pedigrees were collected. Whole exome sequencing and Sanger sequencing were carried out to detect potential variants. RESULTS: The two patients have presented with global developmental delay, coarse facies, muscular hypotonia, congenital heart disease, and pectus excavatum, and were found to harbor two de novo loss-of-function variants of the ARID1B gene, namely c.3586delC (p.Gln1196Serfs*15) and c.4954_4957delACGT (p.Thr1652Glyfs*31). Both variants were unreported previously. CONCLUSION The nonsense variants of the ARID1B gene probably underlay the etiology in these patients. Above finding has enriched the genotypic and phenotypic spectrum of the disease and provided a basis for prenatal diagnosis.
Abnormalities, Multiple ; China ; DNA-Binding Proteins/genetics* ; Face/abnormalities* ; Facies ; Hand Deformities, Congenital/genetics* ; Humans ; Intellectual Disability/genetics* ; Micrognathism/genetics* ; Neck/abnormalities* ; Transcription Factors/genetics*

Jarcho-Levin syndrome (JLS) is a condition manifested by malformations of vertebral bodes and related ribs. There are two major subtypes spondylocostal dysostosis and spondylothoracic dysostosis, with different survival rates, associated malformations, and inheritance patterns. We have experienced an autopsy case of a premature female fetus with multiple congenital anomalies. She was 30 weeks of gestational age, born as the second baby of twins and expired shortly after birth. A post-mortem examination revealed multiple abnormalities including cervicothoracic hemivertebrae, a diminished number of right-sided ribs, and pulmonary hypoplasia with left diaphragmatic hernia. In addition, there were anomalous rotation of the foregut, unfused pancreas and anomalous drainage of the superior vena cava. Chromosomal analysis showed 46, XX, del(4)(q ter).
Abnormalities, Multiple/genetics/*pathology ; Autopsy ; Chromosome Deletion ; Chromosomes, Human, Pair 4 ; Female ; Humans ; Infant, Newborn ; Ribs/*abnormalities ; Spine/*abnormalities ; Syndrome