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1.
JCI Insight ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771644

ABSTRACT

Hypotrichosis is a genetic disorder which characterized by a diffuse and progressive loss of scalp and/or body hair. Nonetheless, the causative genes for several affected individuals remain elusive, and the underlying mechanisms have yet to be fully elucidated. Here, we discovered a dominant variant in ADAM17 gene caused hypotrichosis with woolly hair. Adam17 (p.D647N) knock-in mice model mimicked the hair abnormality in patients. ADAM17 (p.D647N) mutation led to hair follicle stem cells (HFSCs) exhaustion and caused abnormal hair follicles, ultimately resulting in alopecia. Mechanistic studies revealed that ADAM17 binds directly to E3 ubiquitin ligase TRIM47. ADAM17 (p.D647N) variant enhanced the association between ADAM17 and TRIM47, leading to an increase in ubiquitination and subsequent degradation of ADAM17 protein. Furthermore, reduced ADAM17 protein expression affected Notch signaling pathway, impairing the activation, proliferation, and differentiation of HFSCs during hair follicle regeneration. Overexpression of NICD rescued the reduced proliferation ability caused by Adam17 variant in primary fibroblast cells.

2.
Int J Biol Macromol ; 242(Pt 3): 125107, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37257541

ABSTRACT

Ten foxtail millet cultivars with different congee-making quality were investigated for relationships between starch structures, functional properties and congee-making qualities. Swelling power, pasting peak viscosity (PV) and setback (SB), gel hardness and resilience, and gelatinization onset (To), peak (Tp) and range (R) temperature were correlated with congee-making performance significantly. Good eating-quality cultivars with these parameters were in the range of 15.41-18.58 %, 3095-3279 cp, 1540-1745 cp, 430-491 g, 0.47-0.57, 64.43-65.28 °C, 69.97-70.32 °C and 23.38-24.52 °C, respectively. Correlation analysis showed that amylose, amylopectin B2 chains and A21 were essential parameters controlling the functional properties. Amylose molecules with linear molecular morphology would cause crystal defects and a wide range of molecular weight distribution. Additionally, they were more prone to re-association, which influenced the PV, SB, To, Tp and gel hardness. B2 chains impacted the gelatinization temperature range (R), gel resilience and swelling behavior by affecting the alignment of double helices and the size of starch particles and pores. Starch with more binding sites of bound water (A21) tended to leach from the swelling granules easily and contributed to higher values of PV. The content of amylose, B2 chains and A21 of good eating-quality cultivars were 16.19-18.46 %, 11.60-11.69 % and 96.50-97.02 %, respectively.


Subject(s)
Setaria Plant , Starch , Starch/chemistry , Amylose/chemistry , Setaria Plant/chemistry , Amylopectin/chemistry , Viscosity
3.
Plant Cell Rep ; 42(6): 1003-1024, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37012438

ABSTRACT

KEY MESSAGE: This paper sheds light on the evolution and expression patterns of MADS genes in Setaria and Panicum virgatum. SiMADS51 and SiMADS64 maybe involved in the ABA-dependent pathway of drought response. The MADS gene family is a key regulatory factor family that controls growth, reproduction, and response to abiotic stress in plants. However, the molecular evolution of this family is rarely reported. Here, a total of 265 MADS genes were identified in Setaria italica (foxtail millet), Setaria viridis (green millet), and Panicum virgatum (switchgrass) and analyzed by bioinformatics, including physicochemical characteristics, subcellular localization, chromosomal position and duplicate, motif distribution, genetic structure, genetic evolvement, and expression patterns. Phylogenetic analysis was used to categorize these genes into M and MIKC types. The distribution of motifs and gene structure were similar for the corresponding types. According to a collinearity study, the MADS genes have been mostly conserved during evolution. The principal cause of their expansion is segmental duplication. However, the MADS gene family tends to shrink in foxtail millet, green millet, and switchgrass. The MADS genes were subjected to purifying selection, but several positive selection sites were also identified in three species. And most of the promoters of MADS genes contain cis-elements related to stress and hormonal response. RNA-seq and quantitative Real-time PCR (qRT-PCR) analysis also were examined. SiMADS genes expression levels are considerably changed in reaction to various treatments, following qRT-PCR analysis. This sheds fresh light on the evolution and expansion of the MADS family in foxtail millet, green millet, and switchgrass, and lays the foundation for further research on their functions.


Subject(s)
Panicum , Setaria Plant , Setaria Plant/metabolism , Panicum/genetics , Phylogeny , Gene Expression , Evolution, Molecular , Gene Expression Regulation, Plant/genetics
4.
J Mol Model ; 29(5): 134, 2023 Apr 11.
Article in English | MEDLINE | ID: mdl-37041399

ABSTRACT

Magnaporthe oryzae is the causal agent of rice blast, and understanding how abiotic stress affects the resistance of plants to this disease is useful for designing disease control strategies. In this paper, the effects of temperature and microwave irradiation on the effector complex comprising APikL2A from M. oryzae and sHMA25 from foxtail millet were investigated by molecular dynamics simulations using the GROMACS software package. While the structure of APikL2A/sHMA25 remained relatively stable in a temperature range of 290 K (16.85 °C) to 320 K (46.85 °C), the concave shape of the temperature-dependent binding free energy curve indicated that there was maximum binding affinity between APikL2A and sHMA25 at 300 K-310 K. This coincided with the optimum infectivity temperature, thus suggesting that coupling of the two polypeptides may play a role in the infection process. A strong oscillating electric field destroyed the structure of APikL2A/sHMA25, although it was stable and not susceptible to weak electric fields.


Subject(s)
Magnaporthe , Oryza , Temperature , Microwaves , Molecular Dynamics Simulation
5.
Front Plant Sci ; 13: 863298, 2022.
Article in English | MEDLINE | ID: mdl-35755676

ABSTRACT

CCT transcription factors are involved in the regulation of photoperiod and abiotic stress in Arabidopsis and rice. It is not clear that how CCT gene family expand and regulate heading date in foxtail millet. In this study, we conducted a systematic analysis of the CCT gene family in foxtail millet. Thirty-nine CCT genes were identified and divided into four subfamilies based on functional motifs. Analysis showed that dispersed duplication played a predominant role in the expansion of CCT genes during evolution. Nucleotide diversity analysis suggested that genes in CONSTANS (COL)-like, CCT MOTIF FAMILY (CMF)-like, and pseudoresponse response regulator (PRR)-like subfamilies were subjected to selection. Fifteen CCT genes were colocalized with previous heading date quantitative trait loci (QTL) and genome-wide association analysis (GWAS) signals. Transgenic plants were then employed to confirm that overexpression of the CCT gene SiPRR37 delayed the heading date and increased plant height. Our study first investigated the characterization and expansion of the CCT family in foxtail millet and demonstrated the role of SiPRR37. These results lay a significant foundation for further research on the function of CCT genes and provide a cue for the regulation of heading date.

6.
J Dermatol ; 49(9): 921-924, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35567308

ABSTRACT

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus (EN) syndrome, featured by co-occurrence of speckled lentiginous nevus (SLN) and nevus sebaceous (NS). The underlying mechanism has not been clarified. Pathogenic mutations in HRAS, KRAS and BRAF gene are recently recognized as the genetic cause of PPK. Here we present a case of Chinese PPK with a mosaic mutation in HRAS gene. Physical examination of the 4-year-old male proband showed NS locating on the scalp, with EN and SLN on trunk and extremities. Except congenital fundus vascular tortuosity, no evidence of extracutaneous abnormalities was found in this case. A rare heterozygous missense c. 181 C>A mosaic mutation in HRAS was identified in samples from NS, EN and pigmented nevus using next-generation sequencing and Sanger sequencing. Meanwhile, no mutation was found in the non-lesion skin, hair follicle, or blood DNA. Recent breakthrough in clinical manifestation, genetic mutation and prognosis of PPK is also reviewed.


Subject(s)
Nevus, Pigmented , Nevus, Sebaceous of Jadassohn , Nevus , Skin Neoplasms , Child, Preschool , China , Humans , Male , Mosaicism , Nevus/diagnosis , Nevus/genetics , Nevus, Pigmented/pathology , Proto-Oncogene Proteins p21(ras)/genetics , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Skin Neoplasms/pathology
7.
EMBO Mol Med ; 14(5): e14904, 2022 05 09.
Article in English | MEDLINE | ID: mdl-35362222

ABSTRACT

In this report, we discovered a new entity named cataract, alopecia, oral mucosal disorder, and psoriasis-like (CAOP) syndrome in two unrelated and ethnically diverse patients. Furthermore, patient 1 failed to respond to regular treatment. We found that CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane-bound transcription factor peptidase/site-1 protease (MBTPS1, S1P). Mitochondrial abnormalities were observed in patient 1 with CAOP syndrome. Furthermore, we found that S1P is a novel mitochondrial protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB flavination and maintains its stability. Patient S1P variants destabilize ETFA/ETFB, impair mitochondrial respiration, decrease fatty acid ß-oxidation activity, and shift mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis. Mitochondrial dysfunction and inflammatory lesions in patient 1 were significantly ameliorated by riboflavin supplementation, which restored the stability of ETFA/ETFB. Our study discovered that mutations in MBTPS1 resulted in a new entity of CAOP syndrome and elucidated the mechanism of the mutations in the new disease.


Subject(s)
Cataract , Psoriasis , Alopecia/genetics , Cataract/genetics , Electron-Transferring Flavoproteins/genetics , Electron-Transferring Flavoproteins/metabolism , Humans , Riboflavin/metabolism
8.
BMC Pediatr ; 21(1): 314, 2021 07 14.
Article in English | MEDLINE | ID: mdl-34261469

ABSTRACT

BACKGROUND: Eczema is usually the first allergic manifestation to appear in life attributed to gene-environment interactions. IL13, IL4, MS4A2 and ILR4A are four key inflammatory genes associated with atopy. This study aimed to explore gene-environment interactions on eczema in early life among the above four genes and environmental factors in Chinese Han children. METHODS: Five hundred ninety-seven children from a birth cohort who completed two-year follow-up were enrolled and their cord blood was collected. Subjects were genotyped for six polymorphisms in the aforementioned four genes. The children were followed at 6, 12 and 24 months, with epidemiologic information and medical history of eczema collected by questionnaire and eczema assessed by dermatologists. RESULTS: Among the 597 children, 168 were diagnosed with eczema and the others were not after 2 years of follow-up. MS4A2 rs569108 GG genotype (P = 1.68E-02, odds ratio (OR) = 4.66) and antibiotic use (P = 3.75E-4, OR = 2.02) were found independently associated with development of childhood eczema. Children with both antibiotic use and MS4A2 rs569108 GG genotype were more likely to develop eczema than those with only antibiotic use or GG homozygote (OR = 6.24 VS. 2.04 or 4.68). CONCLUSIONS: MS4A2 rs569108 polymorphism and antibiotic use were solely associated with eczema, and they interacted with each other to increase the risk of developing the disease in Chinese Han toddlers. Long-term follow-up along with functional and replication studies are still needed.


Subject(s)
Dermatitis, Atopic , Eczema , Receptors, IgE/genetics , Anti-Bacterial Agents , Cohort Studies , Dermatitis, Atopic/genetics , Eczema/genetics , Humans , Infant , Polymorphism, Genetic , Prospective Studies
9.
Eur J Dermatol ; 31(3): 403-408, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-34309525

ABSTRACT

Atopic dermatitis (AD) can remit as age increases. However, long-term follow-up studies evaluating disease evolution and related factors of persistence of early-onset AD are sparse. This study aimed to identify factors associated with the persistence of early-onset AD. In this prospective cohort study, 260 patients with onset of AD before age two years old were enrolled. Clinical examination was performed and a questionnaire survey completed at enrolment. In addition, the filaggrin gene (FLG) of all participants was sequenced to identify mutations within this gene. Patients were followed at age six and 12. The remission rate was 50.8% at age six and 70.3% at age 12. Persistent AD was associated with a higher SCORAD index at baseline (p < 0.001), a family history of asthma (p = 0.003) and food allergen sensitization (p = 0.033). However, the presence or absence of FLG mutation did not show any significant association with persistent AD. Prognostic factors for persistence of AD were analysed by logistic regression analysis. Disease severity according to SCORAD index at baseline (OR: 1.039; 95% CI: 1.018-1.059; p < 0.001) and family history of asthma (OR: 3.008; 95% CI: 1.297-7.007; p = 0.011) were risk factors that may predict persistent AD based on multivariate regression analysis. It is important to stratify early-onset AD according to severity and investigate family allergic history in order to establish appropriate individual management. Moreover, genetic factors other than FLG mutation may play more important roles in persistent early-onset AD.


Subject(s)
Dermatitis, Atopic/epidemiology , Asthma/epidemiology , Child , Child, Preschool , China/epidemiology , Cohort Studies , Female , Food Hypersensitivity/epidemiology , Genetic Predisposition to Disease , Humans , Male , Prognosis , Risk Factors , Severity of Illness Index
10.
Theor Appl Genet ; 134(9): 3023-3036, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34081150

ABSTRACT

KEY MESSAGE: Multi-environment QTL mapping identified 23 stable loci and 34 co-located QTL clusters for panicle architecture and grain yield-related traits, which provide a genetic basis for foxtail millet yield improvement. Panicle architecture and grain weight, both of which are influenced by genetic and environmental factors, have significant effects on grain yield potential. Here, we used a recombinant inbred line (RIL) population of 333 lines of foxtail millet, which were grown in 13 trials with varying environmental conditions, to identify quantitative trait loci (QTL) controlling nine agronomic traits related to panicle architecture and grain yield. We found that panicle weight, grain weight per panicle, panicle length, panicle diameter, and panicle exsertion length varied across different geographical locations. QTL mapping revealed 159 QTL for nine traits. Of the 159 QTL, 34 were identified in 2 to 12 environments, suggesting that the genetic control of panicle architecture in foxtail millet is sensitive to photoperiod and/or other environmental factors. Eighty-eight QTL controlling different traits formed 34 co-located QTL clusters, including the triple QTL cluster qPD9.2/qPL9.5/qPEL9.3, which was detected 23 times in 13 environments. Several candidate genes, including Seita.2G388700, Seita.3G136000, Seita.4G185300, Seita.5G241500, Seita.5G243100, Seita.9G281300, and Seita.9G342700, were identified in the genomic intervals of multi-environmental QTL or co-located QTL clusters. Using available phenotypic and genotype data, we conducted haplotype analysis for Seita.2G002300 and Seita.9G064000,which showed high correlations with panicle weight and panicle exsertion length, respectively. These results not only provided a basis for further fine mapping, functional studies and marker-assisted selection of traits related to panicle architecture in foxtail millet, but also provide information for comparative genomics analyses of cereal crops.


Subject(s)
Chromosomes, Plant/genetics , Edible Grain/physiology , Gene Expression Regulation, Plant , Phenotype , Plant Proteins/metabolism , Quantitative Trait Loci , Setaria Plant/physiology , Chromosome Mapping/methods , Edible Grain/genetics , Genome, Plant , High-Throughput Nucleotide Sequencing , Plant Proteins/genetics , Polymorphism, Single Nucleotide , Setaria Plant/genetics
11.
Eur J Dermatol ; 31(2): 239-244, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33818390

ABSTRACT

BACKGROUND: Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome comprise a rare genodermatosis associated with biallelic (homozygous or compound heterozygous) mutations in the DSG1 (desmoglein-1) gene, or heterozygous mutations in the DSP (desmoplakin) gene. To date, while many patients with SAM syndrome have been described, the number of cases with SAM syndrome with deep-intronic variants, together its genetic aetiology, remain limited. OBJECTIVES: We report the case of a five-year-old Chinese boy with atypical SAM syndrome. MATERIALS & METHODS: Relevant blood specimens from the family were collected. DNA isolation, RNA isolation and cDNA synthesis, and next-generation sequencing using a multi-gene panel were applied to verify the pathogenic gene. To test the functional consequences and pathogenic mechanism of the deep-intronic mutation in vitro, a mini gene strategy was constructed. RESULTS: A heterozygous DSG1 deletion (c.2437_2450delACCTATCCCTCGGG: p.Tyr814Trpfs*6) and a deep-intronic (c.1688-30A > T) variant were identified. The identified intronic variant was shown to create an alternative splice site, leading to nonsense-mediated mRNA decay of the aberrant transcript. CONCLUSION: This is the first study to demonstrate a causal role for a deep-intronic DSG1 mutation in a patient with SAM syndrome. Our findings underline the need to analyse the intronic regions of DSG1 in patients with SAM syndrome. Improved diagnosis and a better understanding of prognosis will lead to clearer a picture of the concept of atypical SAM syndrome.


Subject(s)
Dermatitis/genetics , Desmoglein 1/genetics , Hypersensitivity/genetics , Metabolic Diseases/genetics , Child, Preschool , Dermatitis/pathology , Desmoglein 1/metabolism , Epidermis/metabolism , Female , Frameshift Mutation , Heterozygote , Humans , Introns , Male , Pedigree , Syndrome
13.
Theor Appl Genet ; 134(5): 1303-1317, 2021 May.
Article in English | MEDLINE | ID: mdl-33566123

ABSTRACT

KEY MESSAGE: Based on the high-density variation map, we identified genome-level evidence for local adaptation and demonstrated that Siprr37 with transposon insertion contributes to the fitness of foxtail millet in the northeastern ecoregion. Adaptation is a robust way through which plants are able to overcome environmental constraints. The mechanisms of adaptation in heterogeneous natural environments are largely unknown. Deciphering the genomic basis of local adaptation will contribute to further improvement in domesticated plants. To this end, we describe a high-depth (19.4 ×) haplotype map of 3.02 million single nucleotide polymorphisms in foxtail millet (Setaria italica) from whole-genome resequencing of 312 accessions. In the genome-wide scan, we identified a set of improvement signals (including the homologous gene of OsIPA1, a key gene controlling ideal plant architecture) related to the geographical adaptation to four ecoregions in China. In particular, based on the genome-wide association analysis results, we identified the contribution of a pseudo-response regulator gene, SiPRR37, to heading date adaptation in foxtail millet. We observed the expression changes of SiPRR37 resulted from a key Tc1-Mariner transposon insertion in the first intron. Positive selection analyses revealed that SiPRR37 mainly contributed to the adaptation of northeastern ecoregions. Taken together, foxtail millet adapted to the northeastern region by regulating the function of SiPRR37, which sheds lights on genome-level evidence for adaptive geographical divergence. Besides, our data provide a nearly complete catalog of genomic variation aiding the identification of functionally important variants.


Subject(s)
Adaptation, Physiological , Gene Expression Regulation, Plant , Genome-Wide Association Study , Plant Proteins/genetics , Polymorphism, Single Nucleotide , Setaria Plant/physiology , Genomics , Phylogeny , Plant Proteins/metabolism , Setaria Plant/genetics
14.
Mol Nutr Food Res ; 65(6): e2000365, 2021 03.
Article in English | MEDLINE | ID: mdl-33480470

ABSTRACT

SCOPE: Millet protein has received much attention due to its beneficial role in alleviating metabolic disease symptoms. This study aims to investigate the role and molecular mechanism of foxtail millet protein isolates, including protein isolates from raw and cooked foxtail millet in alleviating diabetes, including gut microbiota and intracellular signal pathways. METHODS AND RESULTS: Protein isolates from raw and cooked foxtail millet are orally administered to streptozotocin (STZ)-induced diabetic mice for 5 weeks before hypoglycemic effect evaluation. The results show that foxtail millet protein isolates improve glucose intolerance and insulin resistance in diabetic mice. However, only the protein isolate from cooked foxtail millet reverse the weight loss trend and alleviate lipid disorders in diabetic mice. Besides, 16S rRNA sequencing show that both raw and cooked foxtail millet protein isolates altered diabetes-induced gut dysbiosis. In addition, western blotting analysis indicated that the protein isolate from cooked foxtail millet increases the expression levels of glucagon-like peptide-1 receptor (GLP-1R), phosphoinositide 3-kinase (PI3K), and phosphoinositide-protein kinase B (p-AKT)/AKT while the protein isolate from raw foxtail millet downregulates stearoyl-coenzyme A desaturase 1 (SCD1) level. CONCLUSION: Both raw and cooked foxtail millet protein isolates can exert hypoglycemic effects in diabetic mice through rewiring glucose homeostasis, mitigating diabetes-induced gut dysbiosis, and affecting the GLP-1R/PI3K/AKT pathway.


Subject(s)
Diabetes Mellitus, Experimental/diet therapy , Diabetes Mellitus, Type 2/diet therapy , Plant Proteins, Dietary/pharmacology , Setaria Plant/chemistry , Animals , Blood Glucose/metabolism , Cooking , Diabetes Mellitus, Experimental/etiology , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/pathology , Gastrointestinal Microbiome/drug effects , Glucagon-Like Peptide-1 Receptor/metabolism , Hypoglycemic Agents/pharmacology , Insulin Resistance , Male , Mice, Inbred C57BL , Phosphatidylinositol 3-Kinases/metabolism , Plant Proteins, Dietary/isolation & purification , Proto-Oncogene Proteins c-akt/metabolism , Streptozocin
15.
Nutrients ; 12(11)2020 Nov 11.
Article in English | MEDLINE | ID: mdl-33187155

ABSTRACT

Millet proteins have been demonstrated to possess glucose-lowering and lipid metabolic disorder modulation functions against diabetes; however, the molecular mechanisms underlying their anti-diabetic effects remain unclear. The present study aimed to investigate the hypoglycemic effect of prolamin from cooked foxtail millet (PCFM) on type 2 diabetic mice, and explore the gut microbiota and serum metabolic profile changes that are associated with diabetes attenuation by PCFM. Our diabetes model was established using a high-fat diet combined with streptozotocin before PCFM or saline was daily administrated by gavage for 5 weeks. The results showed that PCFM ameliorated glucose metabolism disorders associated with type 2 diabetes. Furthermore, the effects of PCFM administration on gut microbiota and serum metabolome were investigated. 16S rRNA gene sequencing analysis indicated that PCFM alleviated diabetes-related gut microbiota dysbiosis in mice. Additionally, the serum metabolomics analysis revealed that the metabolite levels disturbed by diabetes were partly altered by PCFM. Notably, the decreased D-Glucose level caused by PCFM suggested that its anti-diabetic potential can be associated with the activation of glycolysis and the inhibition of gluconeogenesis, starch and sucrose metabolism and galactose metabolism. In addition, the increased serotonin level caused by PCFM may stimulate insulin secretion by pancreatic ß-cells, which contributed to its hypoglycemic effect. Taken together, our research demonstrated that the modulation of gut microbiota composition and the serum metabolomics profile was associated with the anti-diabetic effect of PCFM.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Plant Extracts/pharmacology , Prolamins/pharmacology , Setaria Plant/chemistry , Animals , Blood Glucose/drug effects , Cooking , Diet, High-Fat , Dysbiosis/drug therapy , Gastrointestinal Microbiome/drug effects , Hypoglycemic Agents/pharmacology , Male , Metabolomics , Mice , Mice, Inbred C57BL , RNA, Ribosomal, 16S/genetics , Streptozocin
16.
Mol Genet Genomic Med ; 8(11): e1457, 2020 11.
Article in English | MEDLINE | ID: mdl-32881395

ABSTRACT

BACKGROUND: Superficial epidermolytic ichthyosis (SEI), known as ichthyosis bullosa of Siemens (IBS; OMIM No. 146800) before, is a type of keratinopathic ichthyosis due to the KRT2 mutations (NM_000423.3; OMIM No. 600194). Here, we report the first case of SEI caused by a KRT2 mosaic mutation. METHODS: We presented the clinical data of a 5-year-old Chinese boy who suffered from SEI. The histopathological examination and immunofluorescence were performed to rule out immunobullous skin diseases and diseases with subepidermal blisters. Genomic DNA samples were extracted from the lesion tissue and next-generation sequencing was performed. We also confirmed the variant allele frequency (VAF) in different tissues by an Ultra-Deep Sequencing technology. RESULTS: The patient presented with blisters on the lower extremities and linear, superficially hyperkeratotic lesions. Immunofluorescence of IgG, IgA, IgM, C3, C4, and C1q were negative, and the histopathological results showed intraepidermal blisters containing lymphocytes and eosinophils. A heterozygous missense mutation, c.G1459A (p. Glu487Lys), in exon 7 of the KRT2 gene was detected at a 31.17% allele frequency. The same mutation p. Glu487Lys has been described several times in the literature. CONCLUSION: Thus, in our patient, the mosaic mutation explains the blaschkoid ichthyosiform phenotype. To our knowledge, this is the first case of SEI with a KRT2 mosaic mutation.


Subject(s)
Hyperkeratosis, Epidermolytic/genetics , Keratin-2/genetics , Mosaicism , Child , Genetic Testing , Heterozygote , High-Throughput Nucleotide Sequencing , Humans , Hyperkeratosis, Epidermolytic/diagnosis , Male , Mutation, Missense , Phenotype , Sequence Analysis, DNA
17.
J Dermatol ; 47(12): 1445-1449, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32901930

ABSTRACT

Autosomal recessive woolly hair/hypotrichosis (ARWH/H) is a rare form of congenital alopecia, which can be caused by mutations in lipase H (LIPH), lysophosphatidic acid receptor 6 (LPAR6/P2RY5) or keratin 25 (KRT25) genes. We present a 32-year-old woman with typical clinical features of ARWH. Hair microscopy was performed to observe differences between the patient's hair and a normal sample. Next-generation sequencing was used to detect pathogenic mutations. Sanger sequencing was used to further confirm the mutations. Abnormal hair appearance was found by hair microscopy. A novel frame-shift mutation (NM_139248: c.686delinsGTAGAACCCAACCTGGCT: p.Asp229fs37X) and a reported mutation (NM_139248: exon6:c.T736A: p.C246S) in LIPH were identified in the patient. All reported mutations related to ARWH of various races were reviewed. Our study provides further evidence of the similarity of ARWH between the Chinese and Japanese population. A novel small-insertion mutation also expands the LIPH mutation spectrum.


Subject(s)
Hair Diseases , Hypotrichosis , Adult , Female , Genes, Recessive , Hair , Hair Diseases/diagnosis , Hair Diseases/genetics , Humans , Hypotrichosis/diagnosis , Hypotrichosis/genetics , Lipase/genetics , Mutagenesis, Insertional , Mutation , Pedigree , Receptors, Lysophosphatidic Acid/genetics
18.
Clin Genet ; 97(5): 770-778, 2020 05.
Article in English | MEDLINE | ID: mdl-31953843

ABSTRACT

Inherited ichthyoses are a heterogeneous group of rare disorders related to over 40 genes. To identify underlying molecular causes in inherited ichthyosis among Chinese and to correlate genotype and phenotype, 35 probands clinically diagnosed inherited ichthyosis, except ichthyosis vulgaris and X-linked ichthyosis, were included in our study. Molecular analysis was performed using next-generation sequencing (NGS) through multi-gene panel testing targeting all ichthyosis-related genes. Genetic variants causative for the ichthyosis were identified in 32 of 35 investigated patients. In all, 43 causative mutations across 12 genes were disclosed, including 16 novel variants. Thirteen keratinopathic ichthyosis, fourteen autosomal recessive congenital ichthyosis (ARCI) including one caused by mutations in SDR9C7, and five syndromic ichthyoses were confirmed. Four probands, with presumptive ARCI, turned out to be keratinopathic ichthyosis (2), neutral lipid storage disease (1), and Sjogren-Larsson syndrome (1), respectively. Next-generation technology has been demonstrated to be an effective tool in diagnosing inherited ichthyosis constituting a diverse group of cornification disorders. Our study further expands mutation spectrum and clinical phenotype associated with inherited ichthyosis in Chinese.


Subject(s)
Ichthyosis/genetics , Oxidoreductases/genetics , Sjogren-Larsson Syndrome/genetics , Adolescent , Child , Child, Preschool , China/epidemiology , Female , Genotype , High-Throughput Nucleotide Sequencing , Humans , Ichthyosis/diagnosis , Ichthyosis/pathology , Infant , Male , Mutation , Phenotype , Sjogren-Larsson Syndrome/diagnosis , Sjogren-Larsson Syndrome/pathology , Young Adult
19.
J Dermatol ; 46(5): 422-425, 2019 May.
Article in English | MEDLINE | ID: mdl-30809829

ABSTRACT

A Chinese female infant presented with ectodermal dysplasia, cleft palate and severe skin erosions at birth. Although all the typical clinical features of ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome were present, the ankyloblepharon was not very marked. We misdiagnosed epidermolysis bullosa and congenital ichthyosiform erythroderma at first and confirmed the diagnosis of AEC syndrome only when she presented with the typical clinical manifestation of recurrent infected scalp erosions at 1 year of age. Mutation analysis of exon 13 of the p63 gene revealed a missense mutation Ile482Thr (c.1445T>C) in the sterile alpha motive domain. In this work we review the clinical features, differential diagnosis and prognosis in AEC syndrome.


Subject(s)
Cleft Lip/diagnosis , Cleft Palate/diagnosis , Diagnostic Errors , Ectodermal Dysplasia/diagnosis , Epidermolysis Bullosa/diagnosis , Eye Abnormalities/diagnosis , Eyelids/abnormalities , Ichthyosiform Erythroderma, Congenital/diagnosis , Transcription Factors/genetics , Tumor Suppressor Proteins/genetics , Biopsy , Cleft Lip/genetics , Cleft Lip/pathology , Cleft Lip/therapy , Cleft Palate/genetics , Cleft Palate/pathology , Cleft Palate/therapy , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia/pathology , Ectodermal Dysplasia/therapy , Epidermolysis Bullosa/pathology , Eye Abnormalities/genetics , Eye Abnormalities/pathology , Eye Abnormalities/therapy , Eyelids/pathology , Female , Genetic Testing , Heterozygote , Humans , Ichthyosiform Erythroderma, Congenital/pathology , Infant, Low Birth Weight , Infant, Newborn , Infant, Premature , Mutation, Missense , Skin/pathology
20.
Eur J Dermatol ; 29(6): 641-646, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31903955

ABSTRACT

BACKGROUND: Neu-Laxova syndrome (NLS) is a rare hereditary disorder featuring intrauterine growth retardation, remarkable oedema with skin restriction, limb contracture, ichthyosis, and craniofacial anomaly. NLS shares multiple overlapping characteristics with several other inheritable refractory diseases: for example, harlequin foetus and restrictive dermopathy. To date, many NLS patients have been described, although the number of NLS cases with clear genetic aetiology remains limited. OBJECTIVES: To characterize the clinical and genetic features of NLS in two Chinese families. MATERIALS AND METHODS: Relevant skin tissue samples, blood specimens, and follow-up data from two unrelated Chinese families with perinatal fatal disorders were collected. To obtain a definitive diagnosis, six genes (ABCA12, LMNA, ZMPSTE24, PHGDH, PSAT1 and PSPH), previously implicated in the pathogenesis of inheritable refractory diseases with similar phenotypic expression to that of the affected members in the two pedigrees, were sequenced. We also performed tandem mass spectrometry, structural protein modelling, and immunohistochemical analysis to further support the genetic findings. RESULTS: New and recurrent missense mutations were identified in two genes (PHGDH and PSAT1) associated with NLS, which further supports the recent findings that NLS is genetically heterogeneous and could result from mutations in genes encoding enzymes of the L-serine biosynthesis pathway. Structural changes in PHGDH and PSAT1 proteins were revealed by molecular modelling. Finally, a tandem mass spectrometry assay and immunohistochemical analysis further corroborated the diagnosis of NLS. CONCLUSION: This study is the first description of PHGDH and PSAT1 mutations in Chinese NLS patients, which strongly implicates them in the pathogenesis of NLS.


Subject(s)
Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Brain Diseases/diagnosis , Brain Diseases/genetics , Fetal Growth Retardation/diagnosis , Fetal Growth Retardation/genetics , Ichthyosis/diagnosis , Ichthyosis/genetics , Limb Deformities, Congenital/diagnosis , Limb Deformities, Congenital/genetics , Microcephaly/diagnosis , Microcephaly/genetics , Phosphoglycerate Dehydrogenase/genetics , Transaminases/genetics , Asian People , Humans , Mutation, Missense , Protein Conformation
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