Notes

Quality regarding reduced next molar impaction by means of miniscrew-supported function: A proposal for a simple group.
To explore the clinical feature, diagnosis and phenotype of Majeed syndrome.

Clinical manifestation, diagnostic process, imaging feature and genetic testing of an ethnic Han Chinese patient with Majeed syndrome were reviewed.

The patient, a 3-year-9-month-old boy, had featured psychomotor retardation and developed bone pain from 8 month on. The child had tenderness of the lower limbs and presented with repeatedly joint swelling and pain accompanied by fever. Physical signs included limb muscle weakening, slightly decreased muscle tone, reduced muscle volume and positive Gower sign. High-throughput sequencing revealed that the child has carried compound heterozygous variants of the LPIN2 gene, including c.1966A>G and c.2534delG. MRI showed multiple lesions in bilateral knee joints and distal middle tibia presenting as patchy SPAIR high signals with unclear edge, in addition with edema of soft tissue surrounding the right distal femur.

Majeed syndrome is characterized by chronic and recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and growth retardation. Surrounding muscle tissue of osteomyelitis may also be involved. The syndrome may also affect the central nervous system, resulting in delayed language and motor development. Discovery of multiple pathological variants of the LPIN2 gene suggested that the clinical phenotype of this syndrome may vary between patients to some extent.
Majeed syndrome is characterized by chronic and recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and growth retardation. Surrounding muscle tissue of osteomyelitis may also be involved. The syndrome may also affect the central nervous system, resulting in delayed language and motor development. Discovery of multiple pathological variants of the LPIN2 gene suggested that the clinical phenotype of this syndrome may vary between patients to some extent.
To review the clinical data of a fetus with false positive result of non-invasive prenatal testing (NIPT) due to confined placental mosaicism (CPM).

Amniotic fluid sample was taken from a pregnant women with high risk for chromosome 16 aneuploidy for karyotyping analysis, single nucleotide polymorphism array (SNP array) and interphase fluorescence in situ hybridization (FISH). Genetic testing was also conducted on the fetal and maternal surface of the placenta, root of umbilical cord and fetal skin tissue after induced abortion.

Cytogenetic analysis of the amniotic fluid sample yielded a normal karyotype. SNP array revealed mosaicism (20%) of trisomy 16 in the fetus. FISH confirmed the presence of mosaicism (25%) for trisomy 16. After induced labor, all sampled sites of placenta were confirmed to contain trisomy 16 by SNP array, while the analysis of fetal skin tissue yielded a negative result.

CPM is an important factor for false positive NIPT result. Prenatal identification of CPM and strengthened pregnancy management are important to reduce adverse pregnancy outcomes.
CPM is an important factor for false positive NIPT result. Prenatal identification of CPM and strengthened pregnancy management are important to reduce adverse pregnancy outcomes.
To carry out genetic testing for a pregnant woman with mild mental retardation, facial dysmorphism, and a history of adverse pregnancies and provide prenatal diagnosis for her.

Routine G-banded karyotyping and single nucleotide polymorphism microarray (SNP-array) analysis were performed on the couple and amniotic fluid sample.

No karyotypic abnormality was found with the couple and amniotic fluid sample. SNP-array analysis showed that the woman has carried a 7.801 Mb microdeletion in 10q22.3q23.2, which involved 18 OMIM genes including CDHR1, BMPR1A, NRG3, GRID1 and LDB3, which are associated with facial abnormalities, developmental retardation, mental retardation and autism. The fetus also carried a 7.819 Mb deletion in the same region, while the father showed no abnormality.

Both the pregnant woman and her fetus have carried a 10q22.3q23.2 microdeletion, which has provided guidance for her subsequent pregnancy.
Both the pregnant woman and her fetus have carried a 10q22.3q23.2 microdeletion, which has provided guidance for her subsequent pregnancy.
To explore the genetic basis for a case of Lamb-Shaffer syndrome.

Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing(WES). Suspected variant was verified by Sanger sequencing.

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).

The c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene probably underlies the Lamb-Shaffer syndrome in this patient.
The c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene probably underlies the Lamb-Shaffer syndrome in this patient.
To explore the genetic basis for a child with moderate non-syndromic hearing loss.

Next generation sequencing was carried out for the child. Co-segregation of the phenotype and candidate variants was verified among his family members by Sanger sequencing.

The child was found to harbor biallelic variants of the OTOGL gene, namely c.2773C>T (p.Arg925Ter) and c.2826C>G (p.Tyr942Ter), which were respectively inherited from his phenotypically normal father and mother. Both variants were predicted to cause premature termination of protein synthesis and be disease causing by MutationTaster software. The c.2826C>G (p.Tyr942Ter) variant has not been recorded in the Human Gene Mutation Database. Based on the guidelines of the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2+PM4+PP3+PP5 and PVS1+PM2+PM4+PP3, respectively).

The c.2773C>T (p.Arg925Ter) and c.2826C>G (p.Tyr942Ter) variants of the OTOGL gene probably underlay the hearing loss in this child.
G (p.Tyr942Ter) variants of the OTOGL gene probably underlay the hearing loss in this child.
To detect pathogenic variant of the FGD1 gene in a boy with Aarskog-Scott syndrome.

Genetic variant was detected by high-throughput sequencing. Suspected variant was verified by Sanger sequencing. The nature and impact of the candidate variant were predicted by bioinformatic analysis.

The child was found to harbor a novel c.1906C>T hemizygous variant of the FGD1 gene, which has led to conversion of Arginine to Tryptophane at codon 636(p.Arg636Trp). The same variant was found in his mother but not father. Based on the American College of Medical Genetics and Genomics guidelines, the c.1906C>T variant of FGD1 gene was predicted to be likely pathogenic(PM1+PM2+PM5+PP2+PP3+PP4).

The novel c.1906C>T variant of the FGD1 gene may underlay the Aarskog-Scott syndrome in this child. Above finding has enabled diagnosis for the boy.
T variant of the FGD1 gene may underlay the Aarskog-Scott syndrome in this child. Above finding has enabled diagnosis for the boy.
Clinical examination and molecular genetic analysis were carried out for one case with special facial features with developmental retardation, hearing impairment and cleft lip and palate.

The intelligence test, hearing test, and MRI test were performed. buy Rottlerin At the same time, the blood were collected to detect the copy number variation of the whole genome with the chromosomal karyotype analysis and the chromosomal microarray analysis (CMA). And the whole exome sequencing (WES) was used to analyze the pathogenic variant.

The children had mild mental retardation and the IQ was 61. There was moderate hearing loss in both ears(left ear 60 dB, right ear 65 dB). And bilateral horizontal hypoplasia of semicircular canal was found by cranial MRI test. No copy number abnormality was found by chromosome karyotype analysis and chromosome microarray analysis in peripheral blood. And whole exome sequencing suggested that there was heterozygous pathogenic variants in KMT2D gene (p.Leu545Argfs*385).

The patient has a peculiar face and multiple system defects, and was diagnosed as Niikawa-Kuroki syndrome type I by KMT2D gene variant. The whole exome sequencing is helpful for the diagnosis of complex genetic diseases.
The patient has a peculiar face and multiple system defects, and was diagnosed as Niikawa-Kuroki syndrome type I by KMT2D gene variant. The whole exome sequencing is helpful for the diagnosis of complex genetic diseases.
To explore the genetic basis for a Chinese patient featuring cleidocranial dysplasia(CCD).

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.

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).

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.
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.
To explore the genetic basis for a Chinese pedigree affected with genetic epilepsy with febrile seizures plus (GEFS+).

Clinical data of the proband and his family members were collected. Following extraction of genomic DNA, the proband was subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the proband and other family members.

The pedigree, including 6 patients with febrile seizures from 3 generations, was diagnosed with typical GEFS+. Among them, 2 had febrile seizures (FS), 1 had febrile seizures plus (FS+), and 3 had febrile seizures with focal seizures. High-throughput sequencing revealed that the proband has carried a heterozygous missense variant of c.4522T>A (p.Tyr1508Asn) of the SCN1A gene. Sanger sequencing confirmed that other five patients and one normal member from the pedigree have also carried the same variant, which yielded a penetrance of 85.7%.

The c.4522T>A (p.Tyr1508Asn) of the SCN1A gene probably underlay the disease in this pedigree. The pattern of inheritance was consistent with autosomal dominant inheritance with incomplete penetrance. Above finding has enriched the variant spectrum of the SCN1A gene.
A (p.Tyr1508Asn) of the SCN1A gene probably underlay the disease in this pedigree. The pattern of inheritance was consistent with autosomal dominant inheritance with incomplete penetrance. Above finding has enriched the variant spectrum of the SCN1A gene.
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