Detection of ATP2C1 gene mutations in a family with generalized familial benign chronic pemphigus / 中华皮肤科杂志

A 60-year-old female proband presented with recurrent erythema, blisters and erosions all over the body for 30 years, which had been aggravated 10 days prior to the presentation. Skin examination showed erythematous swelling of the bilateral eyelids with scattered dark red crusts, scattered erythema and erosions on the nasolabial folds and chin, large areas of erythema and erosions on the neck, bilateral axillae, left cubital fossa, perineum and perianal area, accompanied by bright red granulation tissues and positive Nikolsky′s sign. The proband had two sons, both of whom occasionally presented with erythema and erosions on the axillae and groin, and had not been diagnosed or treated. Blood samples were collected from the proband and her two sons, and genomic DNA was extracted and subjected to whole-exome sequencing. A heterozygous deletion mutation c.955_957del (p.A319del) was identified in the ATP2C1 gene in the proband and her two sons, which had not been previously reported. The patient was finally diagnosed with generalized familial benign chronic pemphigus.

Gene mutation analysis in a Chinese pedigree with autosomal dominant Waardenburg syndrome / 中华皮肤科杂志

Objective:To report a Chinese pedigree with autosomal dominant Waardenburg syndrome, and to identify causative gene mutations.Methods:Clinical data and peripheral blood samples were collected from the proband and her parents. Genomic DNA was extracted, gene mutations were detected through a next-generation skin-targeted sequencing panel, and Sanger sequencing was performed to verify causative mutations.Results:The proband clinically presented with irregular white patches on the abdomen and lower limbs, moderate to severe sensorineural deafness in the right ear, and iris heterochromia in both eyes. The proband′s mother presented with iris heterochromia in both eyes, epicanthus, early canities and thick eyebrows. In the family, both the proband and her mother were diagnosed with Waardenburg syndrome. A causative frameshift mutation c.976-977delinsT (p.Thr327Profs*54) was identified in both the proband and her mother, which caused the AG to TT base substitution at positions 976 - 977 in the coding region of exon 7 of the PAX3 gene, resulted in a frameshift from the amino acid position 327 to 54 in the PAX3 protein (threonine was substituted by proline at amino acid position 327). The proband′s father showed a normal phenotype, and his genetic test results were negative.Conclusion:The novel frameshift mutation c.976-977delinsT (p.Thr327Profs*54) in the PAX3 gene may contribute to the clinical phenotype of the patients with Waardenburg syndrome in the family.

Variation of COL7A1 gene in dystrophic epidermolysis bullosa pruriginosa / 中华医学遗传学杂志

OBJECTIVE@#To perform gene mutation analysis in a Chinese pedigree with dystrophic epidermolysis bullosa pruriginosa (DEB-Pr), and explore phetotype, genotype, and genotypes-phenotypes relationship of DEB-Pr.@*METHODS@#Potential variants of the COL7A1 gene were detected by skin targeted sequencing panel and verified by Sanger sequencing. The pathogenicity of the variation was analyzed.@*RESULTS@#Compound heterozygous variants, c.4128delT and c.8234G>A, were detected in the COL7A1 gene of the two patients. The c.4128delT(p.Pro1376fs) variant was derived from their mother and unreported previously. According to the American College of Medical Genetics and Genomics Standards and Guidelines, it was suggested to be a pathogenic mutation. The c.8234G>A(p.Arg2745Gln) variant was derived from their father, and possibly is a pathogenic variation.@*CONCLUSION@#In this study, the compound heterozygous variants of c.4128delT(p.Pro1376fs) and c.8234G>A(p.Arg2745Gln) of the COL7A1 gene probably underlies the disease in this patient and his sister. And our study expands the database on mutations of DEB-Pr.

Mutation analysis of the ADAR gene in two cases of dyschromatosis symmetrica hereditaria and a survey of their families / 中华皮肤科杂志

Objective:To investigate two Chinese pedigrees with dyschromatosis symmetrica hereditaria (DSH) , and to analyze gene mutations in the pedigrees.Methods:Clinical data were collected from two probands with DSH and other family members in their pedigrees. Peripheral blood samples were obtained from the two probands, their parents and 100 unrelated healthy controls. Gene mutations were detected by using a skin-targeted sequencing panel, and then verified by Sanger sequencing.Results:Case 1, an 18-year-old male patient, presented with millet-sized hyperpigmented and hypopigmented macules scattered on the dorsum of both hands and feet at the age of 5 years, and his mother had similar manifestations. A novel heterozygous frameshift mutation c.1970dupT (p.F657fs) was identified in exon 5 of the ADAR gene in case 1 and his mother, but not found in his father. Case 2, an 8-year-old male patient, presented with mottled rice- to soybean-sized brown hyperpigmented macules and hypopigmented macules on the face and neck, lower back, buttocks, lower limbs, as well as hands and feet, and his father presented with similar manifestations. A known heterozygous frameshift mutation c.2433_2434delAG (p.T811fs) was identified in exon 7 of the ADAR gene in case 2 and his father, but not found in his mother. Neither of the two mutations was identified in the 100 unrelated healthy controls.Conclusion:In this study, a novel mutation c.1970dupT (p.F657fs) in the ADAR gene was identified in a patient with DSH.

Gene mutation analysis in a Chinese pedigree with autosomal recessive woolly hair / 中华皮肤科杂志

Objective:To identify causative genes for autosomal recessive woolly hair (ARWH) in a family.Methods:Clinical data were collected from two patients and other family members in a Chinese pedigree of Han nationality with ARWH. Peripheral blood samples were obtained from the two patients, their unaffected parents and 100 unrelated healthy individuals, and DNA was extracted from the blood samples. A next-generation skin-targeted sequencing panel was used to detect gene mutations in the patients, and Sanger sequencing was performed to verify the sequencing results. The function of protein encoded by the mutant gene was predicted.Results:Two missense mutations c.530T>G (p.Leu177Arg) and c.736T>A (p.Cys246Ser) were both identified in the LIPH gene of the two patients, which were inherited from their father and mother respectively. Neither of the two mutations was identified in the 100 unrelated healthy controls. Interspecies sequence alignment showed that leucine at amino acid position 177 and cysteine at amino acid position 246 of the protein encoded by the LIPH gene were highly evolutionarily conserved. As SIFT and Polyphen-2 softwares showed, the mutations c.530T>G (p.Leu177Arg) and c.736T>A (p.Cys246Ser) were both predicted to be detrimental variations.Conclusion:Two missense mutations c.530T>G (p.Leu177Arg) and c.736T>A (p.Cys246Ser) in the LIPH gene may contribute to the clinical phenotype of the two patients with ARWH in this family.

Genetic testing and genotype-phenotype analysis for a child with X-linked hypohidrotic ectodermal dysplasia / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing for a Chinese patient with X-linked hypohidrotic ectodermal dysplasia (XLHED) and explore its genotype-phenotype correlation.@*METHODS@#Clinical data of the patient was collected. Peripheral blood samples were taken from the patient, his parents and 100 unrelated healthy controls. Genetic variants were detected by using next-generation sequencing using a skin-disease panel through targeted capture and next generation sequencing. Candidate variant was verified by Sanger sequencing. All literature related to genetic testing of XLHED patients in China was searched in the database, and the genotypes and phenotypes of patients in the literature and the correlation between them were statistically analyzed.@*RESULTS@#A novel splice site variant c.655_689del was detected in the patient but not among his parents and the 100 unrelated healthy controls. So far 61 variants of the EDA gene have been identified among Chinese patients with XLHED, which suggested certain degree of genotype-phenotype correlation.@*CONCLUSION@#A novel c.655_689del variant has been identified in the EDA gene, which has expanded the spectrum of EDA gene variant and facilitated delineation of the genotype-phenotype correlation of XLHED.

Two cases of Darier′s disease: ATP2A2 gene mutation analysis and a family survey / 中华皮肤科杂志

Case 1, a 16-year-old male patient, presented with local verrucous hyperplasia and clustered brown follicular keratotic papules on the face, neck and bilateral axillae, some of which merged into plaques; his mother had similar medical history and clinical manifestations. Case 2, a 21-year-old male patient, presented with local verrucous hyperplasia and diffuse follicular keratotic papules on the head, face, neck, trunk, bilateral axillae and buttocks, some of which merged into patchy lesions; none of his family members had similar symptoms. Histopathological examination of the neck skin lesion of the case 2 showed epidermal hyperkeratosis with focal parakeratosis, suprabasal cleft with acantholysis, "villi" , corps ronds and grains in the spinous layer, and inflammatory cells infiltrating the superficial dermis. Genetic testing showed a missense mutation c.2300A>G in exon 15 of the ATP2A2 gene in both the case 1 and his mother, and a splice-region mutation c.2097+5G>A at the junction between exon 15 and intron 15 of the ATP2A2 gene in the case 2. Neither of these mutations were identified in the other family members of the 2 patients.

Short-term efficacy and safety of secukinumab in the treatment of moderate to severe plaque psoriasis: a clinical observation / 中华皮肤科杂志

Objective:To evaluate the short-term clinical efficacy and safety of secukinumab in the treatment of moderate to severe plaque psoriasis.Methods:Thirty-six patients with moderate to severe psoriasis, who visited Department of Dermatology, Henan Provincial People′s Hospital from June 2019 to November 2019, received subcutaneous injection of secukinumab at a dose of 300 mg once a week for 5 weeks, followed by once every 4 weeks. Psoriasis area and severity index (PASI) was recorded at weeks 4, 8 and 12, and adverse drug reactions were observed during the treatment.Results:All the 36 patients received the treatment for at least 12 weeks. At week 4, 8 patients achieved PASI75, including 3 achieving PASI90 and 1 achieving PASI100; at week 8, 26 achieved PASI75, of which 16 achieved PASI90 and 4 achieved PASI100; at week 12, 32 achieved PASI75, of which 26 achieved PASI90 and 8 achieved PASI100. No patients had serious adverse drug reactions, such as severe infections or malignancies. One patient developed abdominal pain and distension after subcutaneous injection in the abdomen, and the symptoms disappeared after 3 days; 1 patient developed tonsillitis followed by eczema-like lesions on the original psoriaitc lesions; suppurative lymphadenitis occurred in the neck of another patient.Conclusion:Secukinumab is markedly effective in the treatment of moderate to severe plaque psoriasis with few adverse effects, and is a new treatment option for patients with moderate to severe plaque psoriasis.

DNA methylation-based subclassification of psoriasis in the Chinese Han population / 医学前沿

Psoriasis (Ps) is an inflammatory skin disease caused by genetic and environmental factors. Previous studies on DNA methylation (DNAm) found genetic markers that are closely associated with Ps, and evidence has shown that DNAm mediates genetic risk in Ps. In this study, Consensus Clustering was used to analyze DNAm data, and 114 Ps patients were divided into three subclassifications. Investigation of the clinical characteristics and copy number variations (CNVs) of DEFB4, IL22, and LCE3C in the three subclassifications revealed no significant differences in gender ratio and in Ps area and severity index (PASI) score. The proportion of late-onset ( ≥ 40 years) Ps patients was significantly higher in type I than in types II and III (P = 0.035). Type III contained the smallest proportion of smokers and the largest proportion of non-smoking Ps patients (P = 0.086). The CNVs of DEFB4 and LCE3C showed no significant differences but the CNV of IL22 significantly differed among the three subclassifications (P = 0.044). This study is the first to profile Ps subclassifications based on DNAm data in the Chinese Han population. These results are useful in the treatment and management of Ps from the molecular and genetic perspectives.

Clinical features and treatments of the neonatal intestinal stenosis after necrotizing enterocolitis / 临床外科杂志

Neonatal necrotizing enterocolitis (NEC) is a common acute abdomen in newborns.Premature infants,especially who have ever involved in infection or anoxia,are quite liable to NEC.NEC is likely to cause intestinal necrosis or intestinal perforation.As the neonatology develops,the survival rate of premature infant and very low birth weight(VLBW) improves too,which at the same time increases the incidence of NEC in newborns.The increasing early diagnosis rate of necrotizing enterocolitis,effective conservative or surgical treatments are saving more and more NEC infants,which also bring higher incidences of NEC complications.Enterostenosis is the most common complication of NEC patient who was given a conservative treatment,and its incidence is as high as 15％ ～ 57 ％.It is difficult to differentiate from feeding difficulties and gastroenteritis due to the lack of specific clinical manifestations in early enterostenosis,which makes the early diagnosis of enterostenosis seems difficult and missed diagnosis or misdiagnosis occurred.Enterostenosis may cause growth retardation,malnutrition or even severe consequences such as enterobrosis,sepsis or death.At present,enterostenosis of NEC has already attracted various medical workers 'attention.Basing on all of the above,our paper took a review on the progress of diagnosis and surgical treatments to enterostenosis.