OBJECTIVE: To explore the clinical and genetic characteristics of a patient with Hermansky-Pudlak syndrome type 5 (HPS-5). METHODS: A child with HPS-5 who had attended the Children's Hospital Affiliated to Shandong University on October 3, 2019 was selected as the study subject. Clinical data of the child were collected. Genetic variant was analyzed through high-throughput sequencing. A literature review was also carried out. RESULTS: The child, a 1-year-and-5-month-old girl, had nystagmus since childhood, lost of retinal pigmentation by fundus examination and easy bruising. High-throughput sequencing revealed that she has harbored compound heterozygous variants of the HPS5 gene, namely c.1562_1563delAA (p.F521Sfs*27) and c.1404C>A (p.C468X), which were inherited from his father and mother, respectively. Based on the guidelines from the American College for Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS+PM2_Supporting+PM3+PP4). Among 18 previously reported HPS-5 patients, all had had eye problems, and most of them had tendency for bleeding. Eight cases had carried compound heterozygous variants of the HPS5 gene, 8 carried homozygous variants, 2 carried double homozygous variants, and most of them were null mutations. CONCLUSION The c.1562_1563delAA(p.F521Sfs*27) and c.1404C>A (p.C468X) compound heterozygous variants of the HPS5 gene probably underlay the HPS-5 in this child. High-throughput sequencing has provided an important tool for the diagnosis. HSP-5 patients usually have typical ocular albinism and/or oculocutaneous albinism and tendency of bleeding, which are commonly caused by compound heterozygous and homozygous variants of the HPS5 gene, though serious complications have been rare.
Female ; Humans ; Infant ; Hermanski-Pudlak Syndrome/pathology* ; High-Throughput Nucleotide Sequencing ; Mutation

Objective:To investigate the status and correlation of 6 weeks postpartum self-compassion, alexithymia and postpartum depression in preterm mothers separated from their infants.Methods:Convenience sampling method was used to select 300 premature mothers separated from their infants in Binzhou Medical University Hospital as the research objects. A cross-sectional survey was conducted by the general data, the Chinese version of the Self-Compassion Scale (SCS-C), the Chinese version of the Toronto Alexithymia Scale (TAS-20) and the Edinburgh Postnatal Depression Scale (EPDS).Results:The total scores of SCS-C, TAS-20 and EPDS at 6 weeks postpartum were (19.94 ± 2.64), (48.74 ± 3.87) and (10.61 ± 3.07) respectively. The self-compassion ability was negatively correlated with alexithymia and postpartum depression ( r = -0.365, -0.313, both P<0.01), alexithymia was positively correlated with postpartum depression ( r = 0.657, P<0.01). Alexithymia played a partial mediating role in the relationship between self-compassion and postpartum depression, accounting for 72.83% of the total effect. Conclusions:Self-compassion and alexithymia are both important factors affecting postpartum depression in premature mothers separated from their infants. By enhancing emotional cognition and processing ability of premature mothers, self-compassion ability can be improved to reduce the incidence of postpartum depression.

Objective : To investigate the pathogenic factors and clinical manifestations of contact stomatitis, and to provide references for its clinical diagnosis and prevention. Methods: The data of 55 subjects with contact stomatitis were analyzed retrospectively, including age, gender, pathogenic factors, type of lesions and site of occurrence. Results: Among the 55 patients, contact stomatitis occurred at all ages, 19 were male, 36 were female, and the ratio of males to females was 1∶1.89. Among 55 patients, 78.18% (43/55) were caused by oral mucosal contact with dental materials: amalgam fillings accounted for 52.73% (29/55), metal crowns accounted for 9.09% (5/55), removable denture plastic bases accounted for 9.09% (5/55), resin fillings accounted for 5.45% (3/55), and alginate impression materials accounted for 1.82% (1/55); 21.82% (12/55) were caused by oral mucosal contact with food and daily necessities. The clinical manifestations of contact stomatitis include lichenoid reaction, erythema and erosion. The most common site of contact stomatitis was the cheek, followed by the tongue, and the lips, and the gingival and palatal areas were relatively rare. In the buccal mucosa, the incidence of lichenoid reaction was 55% (22/40), which was higher than that of erosion (20%) and erythema (25%), and the difference was statistically significant (P < 0.05). For tongue, lip, gingiva and palate, there was no significant difference in the incidence of the three lesion types（P > 0.05）. Conclusion Contact stomatitis occurred at all ages, and there are more female patients than males with contact stomatitis. Dental materials, especially metal and acrylic materials (such as the plastic base of removable dentures, resin fillings, adhesives, and self-setting plastics), are the main pathogenic factors. In buccal mucosa, the incidence of lichenoid reaction is higher.

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

Objective To explore the genetic basis for a neonate featuring global developmental delay.Methods Clinical and laboratory tests were carried out for the patient.Peripheral venous blood samples were collected from the neonate and his parents for the extraction of DNA.Potential variant was detected by using targeted capture and next generation sequencing for a panel of genes associated with nervous system diseases.Suspected variant was validated by Sanger sequencing.Results The nine-month-old boy manifested global developmental delay and was unstable to sit alone and distinguish strangers from acquaintance.Genetic testing revealed two novel variants of the SLC19A3 gene in him,namely c.448G＞ A and c.169C＞T.The amino acids encoded by the two codons are highly conservative,and both variants were predicted to be pathogenic by bioinformatic analysis.Conclusion The compound heterozygous c.448G＞A and c.169C＞T variants probably underlay the onset of disease in the patient.Above finding also enriched the variant spectrum of SLC19A3 gene underlying Biotin-thiamine responsive basal ganglia disease.

Objective: To explore the genetic basis for a child with scoliosis, congenital dislocation of the hip joint and growth retardation by using next generation sequencing (NGS). Methods: Peripheral blood samples were obtained from the proband and his parents. Whole genomic DNA was extracted and subjected to NGS. Suspected variant was predicted by bioinformatic tools and validated by Sanger sequencing. Results: The proband was found to carry compound heterozygous variants c. 494T>C (p.Met165Thr) and c. 848A>G (p.His283Arg) of the CANT1 gene, among which c. 494T>C (p.Met165Thr) was inherited from her father and reported to be pathogenic by HGMD. c. 848A>G (p.His283Arg) was inherited from her mother and was predicted to be likely pathogenic according to the ACMG 2015 guidelines. Conclusion The compound heterozygous variants of c. 494T>C (p.Met165Thr) and c. 848A>G (p.His283Arg) of the CANT1 gene probably underlie the disease in the proband.

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 clinical and genetic features of a Chinese boy with oculocutaneous albinism.

METHODSThe clinical features of the patient were analyzed. The DNA of the patient and his parents was extracted and sequenced by next generation exome capture sequencing. The nature and impact of detected mutation were predicted and validated.

RESULTSThe child has displayed strabismus, poor vision, nystagmus and brown hair. DNA sequencing showed that the patient has carried compound heterozygous mutations of the TYRP1 gene, namely c.1214C>A (p.T405N) and c.1333dupG, which were inherited from his mother and father, respectively. Neither mutation was reported previously.

CONCLUSIONThe child has suffered from oculocutaneous albinism type Ⅲ caused by mutations of the TYRP1 gene.

Albinism, Oculocutaneous ; diagnosis ; genetics ; Amino Acid Sequence ; Base Sequence ; Child, Preschool ; Exome ; genetics ; Family Health ; Female ; Heterozygote ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Male ; Membrane Glycoproteins ; genetics ; Mutation ; Oxidoreductases ; genetics ; Parents