Genetic analysis of PYGL gene variants for a child with Glycogen storage disease VI / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic basis of a patient with glycogen storage disease type VI (GSD-VI).@*METHODS@#Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples of the proband and his parents. Genetic variants were detected by using whole exome sequencing. Candidate variants were verified by Sanger sequencing followed by bioinformatics analysis.@*RESULTS@#The proband presented fasting hypoglycemia, hepatomegaly, growth retardation, transaminitis, metabolic acidosis and hyperlactatemia. Liver biopsy indicated GSD. Novel compound heterozygous PYGL gene variants (c.2089A>G/c.158_160delACT) were detected in the proband. Compound heterozygosity was confirmed by Sanger sequencing of the patient's genomic DNA. Provean and MutationTaster predicted the two variants as deleterious and the variant sites are highly conserved.@*CONCLUSION@#The compound heterozygous variants (c.2089A>G/c.158_160delACT) of PYGL gene probably underlay the GSD in the patient. The two novel variants have expanded the spectrum of PYGL gene variants and provided the basis for genetic counseling of the family.

A case of hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis caused by a mutation in the FAM111B gene / 中华皮肤科杂志

A 2-year- and 2-month-old girl developed recurrent eczema-like rashes 7 days after birth, followed by the occurrence of poikiloderma and hair loss. Cholestasis occurred at the age of 1 month and 10 days, which was improved but serum transaminase levels were elevated after 4 months. The patient usually presented with slight sweating, heat intolerance, and delayed gross motor development. Skin examination showed generalized mottled hypo- and hyper-pigmented patches, especially in the exposed areas, and sparse hair and eyebrows. Her parents had no similar clinical manifestations. Whole-exome sequencing showed a mutation c.1883G>A (p.Ser628Asn) in the FAM111B gene in the child, which was not found in her parents. According to the typical skin lesions, abnormal liver function and genetic testing results, this patient was diagnosed with hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis, and the mutation c.1883G>A in the FAM111B gene may be the cause of the patient′s clinical manifestations. The patient received hepatoprotective therapy, sun screen intervention, rehabilitation training, etc. After 10-month follow-up, the patient still presented with skin lesions and elevated transaminases, but without other discomforts.

Comparative analysis of childhood macrophage activation syndrome and other hemophagocytic syndrome / 中华风湿病学杂志

Objective To compare the clinical features, diagnosis, treatment and prognosis between macrophages activation syndrome (MAS) and other hemophagocytic syndrome (HPS). Methods Thirty-six children with HPS were identified at Nanjing Children's Hospital during January 2006 to March 2009. They could be classi-fied into MAS group (13 patients) and other HPS group (23 patients). All relevant clinical features, laboratory data, treatments and outcomes were analyzed with t test,χ2 test and Fisher's exact test.Results Patients with MAS tended to be elder than those with other HPSs [(7.7±1.3) years vs (2.6±0.5)years, t=3.899, P=0.004]. There was no difference in gender distribution. In MAS cases, the central nervous system (69% vs 13%, P=0.001), circulatory system (23% vs 9%, P=0.047) and the urinary system (38% vs 9%, P=0.033) were usually involved. The clinical symptoms of MAS were more sever than other HPS. Serum ferritin [(9703±9819) μg/L vs (4569±1396) μg/L, t=2.854, P=0.015] and erythrocyte sedimentation rate (ESR) [(53±32) mm/1 h vs (20±14) mm/1 h, t=2.708, P=0.020] changed more obviously in MAS cases compared with other HPS. Conclusion, Childhood MAS is different from other HPS in terms of age, etiology, clinical manifestations, laboratory tests and treatments.