Adult ; Child, Preschool ; Female ; Humans ; Ichthyosis Vulgaris ; genetics ; Infant ; Male ; Mutation ; Pedigree

Research of the FLG mutation in various ethnic groups revealed non-overlapping mutation patterns. In addition, Japanese and Chinese atopic patients showed somewhat different mutations. These ethnic differences make the research on Korean patients mandatory; however, no systematic research on Korean atopic dermatitis (AD) patients has been performed. This study aims to investigate the genetic polymorphism of FLG in Korean atopic dermatitis patients. The study was made up of three groups including 9 Ichthyosis vulgaris (IV) patients, 50 AD patients and 55 normal controls: the ichthyosis group was incorporated due to the reported association between the FLG mutation and IV. In comparison to other sequencing methods, the overlapping long-range PCR was used. We revealed the genetic polymorphism of filaggrin in Koreans, and at the same time, we discovered nonsense mutations in p.Y1767X and p.K4022X in Korean AD patients. By using FLG sequencing techniques confirmed in this study, new mutations or genetic polymorphisms with ethnic characteristics would be detected and further larger studies of repeat number polymorphisms could be performed.
Adult ; Alleles ; Asian Continental Ancestry Group/*genetics ; Base Sequence ; Codon, Nonsense ; DNA/blood/chemistry/metabolism ; DNA Mutational Analysis ; Dermatitis, Atopic/*genetics ; Female ; Genotype ; Heterozygote ; Humans ; Ichthyosis Vulgaris/genetics ; Intermediate Filament Proteins/*genetics ; Male ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide

OBJECTIVETo identify potential mutations of the FLG gene in two Chinese families affected with ichthyosis vulgaris.

METHODSAll coding exons and exon-intron boundary of the FLG gene were amplified by polymerase chain reaction (PCR) and analyzed by direct sequencing. The results were compared with those of 100 unrelated healthy controls.

RESULTSTwo novel missense mutations, c.1360A>G (p.T454A) and c.10363G>T (p.D3455Y), were detected in all affected individuals from family 1 and family 2 respectively but none of the controls.

CONCLUSIONThe c.1360A>G (p.T454A) and c.10363G>T (p.D3455Y) of the FLG gene may lead to alteration of the structure and function of the FLG protein and cause ichthyosis vulgaris in the two families.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA Mutational Analysis ; Exons ; genetics ; Family Health ; Female ; Genetic Predisposition to Disease ; ethnology ; genetics ; Humans ; Ichthyosis Vulgaris ; ethnology ; genetics ; Intermediate Filament Proteins ; genetics ; Introns ; genetics ; Male ; Mutation, Missense ; Pedigree

Adult ; China ; Female ; Humans ; Ichthyosis Vulgaris ; diagnosis ; genetics ; Male ; Middle Aged ; Pedigree ; Young Adult

OBJECTIVETo detect FLG gene mutations in 10 families affected with ichthyosis vulgaris and to explore mutational hot spot of the FLG gene in Chinese Han population.

METHODSPCR and direct sequencing were carried out to identify potential mutations of the FLG gene in above families. One hundred healthy individuals were analyzed as normal controls.

RESULTSThree mutations (3321delA, 5757delCCAG and S2706X) were identified in 7 families. A homozygous mutation 3321delA was also detected in two unrelated patients. No mutations were found in the remaining three families. Neither of the null mutations (5757delCCAG and S2706X) was found in the 100 controls. However, for 3321delA, a heterozygous mutation was also found in two of the controls.

CONCLUSIONThree FLG mutations have been identified in the selected families with ichthyosis vulgaris, and the 3321delA mutation was most prevalent (46.9%). Mutations 5757delCCAG and S2706X were first found in patients with ichthyosis vulgaris. Other candidate genes may underlie the disease in those without a FLG mutation.

Asian Continental Ancestry Group ; Base Sequence ; China ; Female ; Genotype ; Humans ; Ichthyosis Vulgaris ; genetics ; Intermediate Filament Proteins ; genetics ; Male ; Mutation ; Pedigree ; Phenotype

Pityriasis rotunda is an uncommon dermatosis characterized by asymptomatic, multiple, widely distributed, round or oval-shaped, hyperpigmented or hypopigmented, fine, scaly patches. They typically involve the abdomen, the trunk and extremities. Histopathologic findings are consistent with ichthyosis vulgaris, such as hyperkeratosis, hypogranulosis or agranulosis, hyperpigmentation of the basal layer in epidermis, and perivascular lymphohistiocytic infiltration in the dermis. Although the etiology of the disease remains unknown, it has been associated with a variety of underlying systemic diseases including infectious diseases, hormonal disorders, malignancies, and chronic disorders. One clinical case has been reported about the occurrence of the disease during pregnancy of a 24-year-old african woman, but there is only one reported case of exacerbation of the disease during pregnancy in Korea. Herein, we report a case of pityriasis rotunda occurring during pregnancy.
Abdomen ; Communicable Diseases ; Dermis ; Epidermis ; Extremities ; Female ; Humans ; Hyperpigmentation ; Ichthyosis Vulgaris ; Korea ; Pityriasis ; Pregnancy ; Skin Diseases ; Young Adult

Pityriasis rotunda (PR) is a rare disease characterized by persistent, sharply defined, oval, scaly patches of dry skin, localized mainly on the trunk and extremities. Its etiology remains unknown. However, several reports suggest that it is a form of acquired ichthyosis vulgaris or a skin manifestation of systemic disease, such as malnutrition, chronic illness, hepatic disease, and malignancies. Although a variety of treatment modalities, including topical lactic acid, urea, tars, emollients, and corticosteroid, have been applied to it, their efficacies are not satisfactory. Herein, we report a case of PR in a healthy man who was successfully treated with oral and topical retinoids.
Chronic Disease ; Emollients ; Extremities ; Ichthyosis ; Ichthyosis Vulgaris ; Lactic Acid ; Malnutrition ; Pityriasis ; Rare Diseases ; Retinoids ; Skin ; Skin Manifestations ; Tars ; Urea

Pityriasis rotunda (PR) is a rare disease characterized by persistent, sharply defined, oval, scaly patches of dry skin, localized mainly on the trunk and extremities. Its etiology remains unknown. However, several reports suggest that it is a form of acquired ichthyosis vulgaris or a skin manifestation of systemic disease, such as malnutrition, chronic illness, hepatic disease, and malignancies. Although a variety of treatment modalities, including topical lactic acid, urea, tars, emollients, and corticosteroid, have been applied to it, their efficacies are not satisfactory. Herein, we report a case of PR in a healthy man who was successfully treated with oral and topical retinoids.
Chronic Disease ; Emollients ; Extremities ; Ichthyosis ; Ichthyosis Vulgaris ; Lactic Acid ; Malnutrition ; Pityriasis ; Rare Diseases ; Retinoids ; Skin ; Skin Manifestations ; Tars ; Urea

BACKGROUND: Filaggrin is a key protein that facilitates the formation of skin barrier by forming a stratum corneum. Mutations in the gene encoding filaggrin (FLG) have recently been reported in patients with ichthyosis vulgaris (IV). Interestingly, there are ethnic differences between FLG mutations identified in Asians and Europeans, and few FLG mutations are overlapping between Chinese and Japanese IV patients. OBJECTIVE: The aim of this study was to investigative the genetic polymorphism of FLG in Korean IV patients. METHODS: Genomic DNA was extracted from whole venous blood specimen of Korean patients with IV and a control group, and the full sequence of FLG was determined via overlapping long-range polymerase chain reaction method. RESULTS: Analysis of base sequence previously unreported reveal new nonsense mutation p.Y1767X in a Korean IV patient, and additional new single nucleotide polymorphisms. CONCLUSION: On the basis of this study, it is anticipated that analysis of FLG gene sequence be extended to other dermatoses associated with FLG, such as atopic dermatitis.
Asian Continental Ancestry Group ; Base Sequence ; Codon, Nonsense ; Dermatitis, Atopic ; DNA ; Humans ; Ichthyosis ; Ichthyosis Vulgaris ; Intermediate Filament Proteins ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Skin ; Skin Diseases

OBJECTIVETo study clinical features of 3 children who presented with nephrotic syndrome (NS) associated with ichthyosis vulgaris (IV), and to detect relationship between NS associated with IV in patients and FLG gene or NPHS2 gene.

METHODClinical and kidney pathological data of the 3 patients were analyzed and progress of pathologic damage in the patient kidney was observed through repeated percutaneous renal biopsy. Using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing, the diversity of the expression of NPHS2 gene in the 3 patients were analyzed, and FLG gene in the 3 patients and parts of their family members with IV was detected.

RESULT(1) The age of the 3 patients (patient 1 was a girl and patients 2 and 3 were boys) suffering from NS was 3 years and 8 months, 2 years and 6 months, and 5 years and 3 months, respectively. The age of onset of IV was 1 year and 6 months, 10 months, and 2 years and 6 months, respectively. All the 3 patients were resistant to steroid therapy. Despite multi-immunosuppressive therapy, no clinical response was achieved. The patients were followed up for 1.5 to 4.0 years. The patients displayed continuous proteinuria, renal function was normal, but their heights were lower than other children at the same age. (2) The older brother of patient 1 died of uremia. The other patients' family members did not have kidney disease. (3) Renal histopathology showed that the patients 1 and 2 had mild mesangial proliferative glomerulonephritis (MsPGN) and the patient 3 had minimal change disease (MCD). One and a half years after the first renal biopsy, the patients 1 and 2 underwent repeated renal biopsy. Renal histopathology showed that the 2 patients' disease developed to medium MsPGN. (4) None of the 3 patients had NPHS2 gene mutation. All the three patients had R501X and 2282del4 which are the common gene mutation type of the FLG, and all the patients were heterozygote. With the detection of the FLG gene of the part of the patients of the three families, the second patient's grandfather had the R501X homozygote mutation and the others were the R501X heterozygote mutation and 2282del4 heterozygote mutation.

CONCLUSIONThe 3 cases of NS associated with IV had no response to steroid and multi-immunosuppressive therapy, the renal damage observed by histopathology progressed fast. The children with NS associated with IV displayed R501X heterozygote mutation and 2282del4 heterozygote mutation of FLG gene, which suggested that the absence of response to steroid and multi-immunosuppressive therapy may be related to the FLG gene.

Child, Preschool ; DNA Mutational Analysis ; Female ; Humans ; Ichthyosis Vulgaris ; complications ; genetics ; Infant ; Intracellular Signaling Peptides and Proteins ; genetics ; Kidney ; pathology ; Male ; Membrane Proteins ; genetics ; Mutation ; Nephrotic Syndrome ; complications ; genetics ; Pedigree