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1.
Int J Dermatol ; 58(8): 946-952, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31077348

RESUMO

BACKGROUND: Autosomal recessive wooly hair/hypotrichosis is an inherited disorder of hair characterized by less dense, short, and tightly curled hair on the scalp and sometimes less dense to complete absence of eyebrows and eyelashes. Autosomal recessive wooly hair/hypotrichosis phenotypes are mostly associated with pathogenic sequence variants in LIPH and LPAR6 genes. METHODS: To find out the molecular basis of the disease, five families with autosomal recessive wooly hair/hypotrichosis were recruited for genetic analysis. Direct Sanger sequencing of LIPH and LPAR6 genes was carried out using BigDye chain termination chemistry. P2RY5 protein homology models were developed to study the effect of mutation on protein structure in a family having novel mutation. RESULTS: Sanger sequencing revealed a novel homozygous missense mutation (c.47A>T) in the LPAR6 gene in family A, while recurrent mutation (c.436G>A) was detected in the rest of the four families (B-E). Protein homology models for both native and mutant P2RY5 protein were developed to study the difference in subtle structural features because of Lys16Met (K16M) mutation. We observed that P2RY5K16M mutation results decrease in the number of ionic interactions detrimental to the protein stability. Protein modeling studies revealed that the novel mutation identified here decreased the number of ionic interactions by affecting physicochemical parameters of the protein, leading to an overall decrease in protein stability with no major secondary structural changes. CONCLUSION: The molecular analysis further confirms the frequent involvement of LPAR6 in autosomal recessive wooly hair/hypotrichosis, while the bioinformatic study revealed that the missense mutation destabilizes the overall structure of P2RY5 protein.


Assuntos
Genes Recessivos/genética , Doenças do Cabelo/genética , Cabelo/anormalidades , Hipotricose/genética , Receptores de Ácidos Lisofosfatídicos/genética , Biologia Computacional , Consanguinidade , Feminino , Humanos , Masculino , Mutação de Sentido Incorreto , Paquistão , Linhagem , Fenótipo , Estrutura Secundária de Proteína/genética , Receptores de Ácidos Lisofosfatídicos/química , Receptores Purinérgicos P2/química , Receptores Purinérgicos P2/genética , Homologia de Sequência de Aminoácidos
2.
Medicina (Kaunas) ; 55(3)2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30934652

RESUMO

The term congenital hypopigmentary disorders refers to a wide group of heterogeneous hereditary diseases, clinically characterized by inborn pigmentary defects of the iris, hair, and/or skin. They include Gray Hair Syndromes (GHSs), a rare group of autosomal recessive genodermatosis hallmarked by inborn silvery gray hair. GHSs encompass Griscelli, Chediak⁻Higashi, Elejalde, and Cross syndromes, which are all characterized by a broad spectrum of severe multisystem disorders, including neurological, ocular, skeletal, and immune system impairment. In this manuscript, we describe in detail the clinical, trichoscopic, and genetic features of a rare case of Griscelli syndrome; moreover, we provide an overview of all the GHSs known to date. Our report highlights how an accurate clinical examination with noninvasive methods, like trichoscopy, may play a crucial rule in diagnosis of rare and potentially lethal genetic syndromes such as Griscelli syndrome, in which timely diagnosis and therapy may modify the clinical course, quality of life, and likelihood of survival.


Assuntos
Transtornos da Pigmentação/diagnóstico , Transtornos da Pigmentação/genética , Doenças Raras/diagnóstico , Doenças Raras/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/imunologia , Anormalidades Múltiplas/patologia , Adulto , Síndrome de Chediak-Higashi/diagnóstico , Síndrome de Chediak-Higashi/genética , Síndrome de Chediak-Higashi/imunologia , Síndrome de Chediak-Higashi/patologia , Pré-Escolar , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/imunologia , Anormalidades Craniofaciais/patologia , Diagnóstico Diferencial , Feminino , Cabelo/anormalidades , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/imunologia , Perda Auditiva Neurossensorial/patologia , Humanos , Hipertricose/induzido quimicamente , Iris/anormalidades , Masculino , Mutação , Síndromes Neurocutâneas/diagnóstico , Síndromes Neurocutâneas/genética , Síndromes Neurocutâneas/imunologia , Síndromes Neurocutâneas/patologia , Piebaldismo/diagnóstico , Piebaldismo/genética , Piebaldismo/imunologia , Piebaldismo/patologia , Transtornos da Pigmentação/imunologia , Transtornos da Pigmentação/patologia , Qualidade de Vida , Doenças Raras/imunologia , Doenças Raras/patologia , Anormalidades da Pele , Proteínas rab27 de Ligação ao GTP/genética
4.
J Clin Immunol ; 39(1): 81-89, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30607663

RESUMO

The association of immunodeficiency-related vaccine-derived rubella virus (iVDRV) with cutaneous and visceral granulomatous disease has been reported in patients with primary immunodeficiency disorders (PIDs). The majority of these PID patients with rubella-positive granulomas had DNA repair disorders. To support this line of inquiry, we provide additional descriptive data on seven previously reported patients with Nijmegen breakage syndrome (NBS) (n = 3) and ataxia telangiectasia (AT) (n = 4) as well as eight previously unreported patients with iVDRV-induced cutaneous granulomas and DNA repair disorders including NBS (n = 1), AT (n = 5), DNA ligase 4 deficiency (n = 1), and Artemis deficiency (n = 1). We also provide descriptive data on several previously unreported PID patients with iVDRV-induced cutaneous granulomas including cartilage hair hypoplasia (n = 1), warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome (n = 1), MHC class II deficiency (n = 1), Coronin-1A deficiency (n = 1), X-linked severe combined immunodeficiency (X-SCID) (n = 1), and combined immunodeficiency without a molecular diagnosis (n = 1). At the time of this report, the median age of the patients with skin granulomas and DNA repair disorders was 9 years (range 3-18). Cutaneous granulomas have been documented in all, while visceral granulomas were observed in six cases (40%). All patients had received rubella virus vaccine. The median duration of time elapsed from vaccination to the development of cutaneous granulomas was 48 months (range 2-152). Hematopoietic cell transplantation was reported to result in scarring resolution of cutaneous granulomas in two patients with NBS, one patient with AT, one patient with Artemis deficiency, one patient with DNA Ligase 4 deficiency, one patient with MHC class II deficiency, and one patient with combined immunodeficiency without a known molecular etiology. Of the previously reported and unreported cases, the majority share the diagnosis of a DNA repair disorder. Analysis of additional patients with this complication may clarify determinants of rubella pathogenesis, identify specific immune defects resulting in chronic infection, and may lead to defect-specific therapies.


Assuntos
Reparo do DNA/genética , Granuloma/complicações , Granuloma/virologia , Síndromes de Imunodeficiência/complicações , Vírus da Rubéola/patogenicidade , Dermatopatias/etiologia , Dermatopatias/virologia , Adolescente , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/virologia , Criança , Pré-Escolar , Feminino , Granuloma/genética , Cabelo/anormalidades , Cabelo/virologia , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hirschsprung/genética , Doença de Hirschsprung/virologia , Humanos , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/virologia , Masculino , Síndrome de Quebra de Nijmegen/genética , Síndrome de Quebra de Nijmegen/virologia , Osteocondrodisplasias/congênito , Osteocondrodisplasias/genética , Osteocondrodisplasias/virologia , Rubéola (Sarampo Alemão)/genética , Rubéola (Sarampo Alemão)/virologia , Pele/virologia , Dermatopatias/genética , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/genética , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/virologia
5.
Skin Res Technol ; 25(4): 447-455, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30614573

RESUMO

OBJECTIVES: To investigate the characteristics of hairs in Female pattern hair loss (FPHL) patients and healthy females in Southern China. MATERIALS AND METHODS: Three fundamental hair parameters in different scalp areas of 90 Southern Chinese FPHL patients and 83 healthy controls were analyzed by phototrichogram. RESULTS: Female pattern hair loss patients showed reduced hair density, hair diameter, and terminal/vellus hair ratio. The reduction correlated with the severity of Ludwig staging. Midscalp was the most affected area in FPHL, but occipital and temporal sites were also involved. In normal women, the highest hair density was observed in midscalp, followed by occipital and temporal areas. Peak hair density at midscalp sites was reached at 20s group, then declined with age. Maximum hair diameter at midscalp and occipital sites occurred in 40s group. Terminal/vellus hair ratio tended to increase with age and peak on 50-60s group. CONCLUSION: Reduced hair density and hair diameter, and miniaturization of hair follicles are the characteristics of FPHL in Southern Chinese women. Occipital and temporal sites are also affected in FPHL. Age-associated changes might have an influence on the hair condition. The values of hair parameters obtained in this study will help to establish reference data for better evaluation of hair disorders.


Assuntos
Alopecia/classificação , Folículo Piloso/crescimento & desenvolvimento , Couro Cabeludo/diagnóstico por imagem , Adulto , Alopecia/patologia , Grupo com Ancestrais do Continente Asiático/etnologia , Contagem de Células , Feminino , Cabelo/anormalidades , Cabelo/citologia , Cabelo/crescimento & desenvolvimento , Folículo Piloso/diagnóstico por imagem , Folículo Piloso/patologia , Humanos , Pessoa de Meia-Idade , Couro Cabeludo/patologia , Índice de Gravidade de Doença
7.
Front Immunol ; 9: 2468, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410491

RESUMO

Background: Mutations in RMRP, encoding a non-coding RNA molecule, underlie cartilage-hair hypoplasia (CHH), a syndromic immunodeficiency with multiple pathogenetic mechanisms and variable phenotype. Allergy and asthma have been reported in the CHH population and some patients suffer from autoimmune (AI) diseases. Objective: We explored AI and allergic manifestations in a large cohort of Finnish patients with CHH and correlated clinical features with laboratory parameters and autoantibodies. Methods: We collected clinical and laboratory data from patient interviews and hospital records. Serum samples were tested for a range of autoantibodies including celiac, anti-cytokine, and anti-21-hydroxylase antibodies. Nasal cytology samples were analyzed with microscopy. Results: The study cohort included 104 patients with genetically confirmed CHH; their median age was 39.2 years (range 0.6-73.6). Clinical autoimmunity was common (11/104, 10.6%) and included conditions previously undescribed in subjects with CHH (narcolepsy, psoriasis, idiopathic thrombocytopenic purpura, and multifocal motor axonal neuropathy). Patients with autoimmunity more often had recurrent pneumonia, sepsis, high immunoglobulin (Ig) E and/or undetectable IgA levels. The mortality rates were higher in subjects with AI diseases ( χ ( 2 ) 2 = 14.056, p = 0.0002). Several patients demonstrated serum autoantibody positivity without compatible symptoms. We confirmed the high prevalence of asthma (23%) and allergic rhinoconjunctivitis (39%). Gastrointestinal complaints, mostly persistent diarrhea, were also frequently reported (32/104, 31%). Despite the history of allergic rhinitis, no eosinophils were observed in nasal cytology in five tested patients. Conclusions: AI diseases are common in Finnish patients with CHH and are associated with higher mortality, recurrent pneumonia, sepsis, high IgE and/or undetectable IgA levels. Serum positivity for some autoantibodies was not associated with clinical autoimmunity. The high prevalence of persistent diarrhea, asthma, and symptoms of inflammation of nasal mucosa may indicate common pathways of immune dysregulation.


Assuntos
Doenças Autoimunes/imunologia , Cabelo/anormalidades , Doença de Hirschsprung/imunologia , Hipersensibilidade/imunologia , Síndromes de Imunodeficiência/imunologia , Osteocondrodisplasias/congênito , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Finlândia/epidemiologia , Cabelo/imunologia , Doença de Hirschsprung/epidemiologia , Doença de Hirschsprung/genética , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/genética , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/genética , Lactente , Masculino , Pessoa de Meia-Idade , Mutação/genética , Osteocondrodisplasias/epidemiologia , Osteocondrodisplasias/genética , Osteocondrodisplasias/imunologia , Prevalência , Estudos Prospectivos , RNA Longo não Codificante/genética , Adulto Jovem
8.
Am J Hum Genet ; 103(5): 777-785, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30401459

RESUMO

Hypotrichosis simplex (HS) is a rare form of hereditary alopecia characterized by childhood onset of diffuse and progressive scalp and body hair loss. Although research has identified a number of causal genes, genetic etiology in about 50% of HS cases remains unknown. The present report describes the identification via whole-exome sequencing of five different mutations in the gene LSS in three unrelated families with unexplained, potentially autosomal-recessive HS. Affected individuals showed sparse to absent lanugo-like scalp hair, sparse and brittle eyebrows, and sparse eyelashes and body hair. LSS encodes lanosterol synthase (LSS), which is a key enzyme in the cholesterol biosynthetic pathway. This pathway plays an important role in hair follicle biology. After localizing LSS protein expression in the hair shaft and bulb of the hair follicle, the impact of the mutations on keratinocytes was analyzed using immunoblotting and immunofluorescence. Interestingly, wild-type LSS was localized in the endoplasmic reticulum (ER), whereas mutant LSS proteins were localized in part outside of the ER. A plausible hypothesis is that this mislocalization has potential deleterious implications for hair follicle cells. Immunoblotting revealed no differences in the overall level of wild-type and mutant protein. Analyses of blood cholesterol levels revealed no decrease in cholesterol or cholesterol intermediates, thus supporting the previously proposed hypothesis of an alternative cholesterol pathway. The identification of LSS as causal gene for autosomal-recessive HS highlights the importance of the cholesterol pathway in hair follicle biology and may facilitate novel therapeutic approaches for hair loss disorders in general.


Assuntos
Genes Recessivos/genética , Transferases Intramoleculares/genética , Mutação/genética , Adolescente , Adulto , Alelos , Alopecia/genética , Colesterol/genética , Retículo Endoplasmático/genética , Feminino , Cabelo/anormalidades , Doenças do Cabelo/genética , Humanos , Hipotricose/genética , Queratinócitos/patologia , Masculino , Linhagem , Adulto Jovem
10.
Orphanet J Rare Dis ; 13(1): 207, 2018 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-30445974

RESUMO

BACKGROUND: Patients with cartilage-hair hypoplasia (CHH), a rare metaphyseal chondrodysplasia, manifest severe growth failure, variable immunodeficiency and increased risk of malignancies. The impact of CHH on gynecologic and reproductive health is unknown. Vulnerability to genital infections may predispose CHH patients to prolonged human papillomavirus (HPV) infections potentially leading to cervical, vaginal and vulvar cancer. METHODS: We carried out gynecologic evaluation, pelvic ultrasound and laboratory assessment in 19 women with genetically confirmed CHH. All patients were clinically examined and retrospective data were collected from hospital records. RESULTS: The women ranged in age from 19.2 to 70.8 years (median 40.8 years) and in height from 103 to 150 cm (median 123 cm). All women had undergone normal pubertal development as assessed by breast development according to Tanner scale and by age of menarche (mean 12.5 yrs., range 11-14 yrs). Despite significant short stature and potentially small pelvic diameters, a well-developed uterus with fairly normal size and shape was found by pelvic ultrasound in most of the patients. Ovarian follicle reserve, assessed by ultrasound was normal in relation to age in all premenopausal women it could be assessed (12 cases). Anti-Müllerian hormone was normal in relation to age in 17 women (89%). HPV was detected in 44% (8/18) and three women carried more than one HPV serotype; findings did not associate with immunological parameters. Three patients had a concurrent cell atypia in Pap smear. CONCLUSIONS: Pubertal development, reproductive hormones and ovarian structure and function were usually normal in women with CHH suggesting fairly normal reproductive health. However, the immunodeficiency characteristic to CHH may predispose the patients to HPV infections. High prevalence of HPV infections detected in this series highlights the importance of careful gynecologic follow up of these patients.


Assuntos
Cabelo/anormalidades , Doença de Hirschsprung/patologia , Doença de Hirschsprung/virologia , Síndromes de Imunodeficiência/patologia , Síndromes de Imunodeficiência/virologia , Osteocondrodisplasias/congênito , Papillomaviridae/patogenicidade , Adulto , Idoso , Feminino , Genótipo , Cabelo/patologia , Cabelo/virologia , Doença de Hirschsprung/genética , Humanos , Síndromes de Imunodeficiência/genética , Pessoa de Meia-Idade , Osteocondrodisplasias/genética , Osteocondrodisplasias/patologia , Osteocondrodisplasias/virologia , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Estudos Retrospectivos , Sorogrupo
12.
Turk J Pediatr ; 60(1): 89-93, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30102486

RESUMO

Akgün-Dogan Ö, Simsek-Kiper PÖ, Utine GE, Boduroglu K. Anauxetic dysplasia: A rare clinical entity. Turk J Pediatr 2018; 60: 89-93. Cartilage hair hypoplasia and anauxetic dysplasia spectrum constitute a group of autosomal recessive disorders characterized by variable extent of metaphyseal to spondylometaepiphyseal involvement and various additional clinical features. Within this group, anauxetic dysplasia represents the severe end of the skeletal spectrum. However, extraskeletal features including immunodeficiency, hematological abnormalities, and hair hypoplasia are absent, despite the severe skeletal involvement. This disorder is caused by mutations in the gene encoding ribonuclease mitochondrial RNA-processing complex. We herein report on a patient with anauxetic dysplasia, who presented with severe roto-scoliosis and skeletal findings requiring surgical intervention, and in whom a homozygous RMRP mutation was detected.


Assuntos
Nanismo/genética , Mutação , Osteocondrodisplasias/genética , Criança , Nanismo/diagnóstico por imagem , Feminino , Cabelo/anormalidades , Doença de Hirschsprung/genética , Homozigoto , Humanos , Síndromes de Imunodeficiência/genética , Osteocondrodisplasias/congênito , Osteocondrodisplasias/diagnóstico por imagem , Radiografia , Escoliose/diagnóstico por imagem
14.
Clin Exp Dermatol ; 43(6): 713-717, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29744913

RESUMO

Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia characterized by short-stature, sparse hair and impaired cellular immunity. We describe a young girl who was diagnosed with CHH based on the findings of recurrent infections, short stature with metaphyseal chondrodysplasia, and a confirmed bi-allelic RMRP gene mutation. At 13 years, the patient developed an Epstein-Barr virus (EBV)-driven lymphoproliferative disorder involving the lung, which responded partially to chemotherapy. Simultaneously, she developed multiple indurated plaques involving her face, which had histological findings of granulomatous inflammation and EBV-associated low-grade lymphomatoid granulomatosis. The patient received a matched unrelated peripheral blood stem cell transplant at 15 years of age, and her immunological parameters and skin lesions improved. Lymphomatoid forms of granulomatosis and cutaneous EBV-associated malignancies have not been described previously in CHH. This case highlights the possibility of EBV-associated cutaneous malignancy in CHH.


Assuntos
Cabelo/anormalidades , Doença de Hirschsprung/complicações , Síndromes de Imunodeficiência/complicações , Neoplasias Pulmonares/complicações , Pulmão/patologia , Granulomatose Linfomatoide/complicações , Osteocondrodisplasias/congênito , Neoplasias Cutâneas/complicações , Adolescente , Feminino , Herpesvirus Humano 4/isolamento & purificação , Doença de Hirschsprung/terapia , Humanos , Síndromes de Imunodeficiência/terapia , Pulmão/virologia , Neoplasias Pulmonares/patologia , Granulomatose Linfomatoide/patologia , Osteocondrodisplasias/complicações , Osteocondrodisplasias/terapia , Transplante de Células-Tronco
15.
Swiss Med Wkly ; 148: w14606, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29688570

RESUMO

Cartilage hair hypoplasia (CHH) is a rare autosomal recessive ribosomopathy characterised by skeletal and integumentary system manifestations. It may also present with varied forms and intensities of haematopoietic and/or immune disorders. We report a 27-year-old female who presented a picture of combined immunodeficiency after receiving an adriamycin-based chemotherapy regimen followed by autologous stem cell transplantation. Her medical history indicated neonatal dwarfism, recurrent ear, nose and throat and respiratory infections, and hypogammaglobulinaemia, which were suggestive of a primary minor B-cell immune deficiency. Taken together, the diagnosis of cartilage hair hypoplasia was suspected and confirmed by means of molecular biological analysis. Here, we discuss the causal relationship and molecular mechanisms existing between both primary immunodeficiency and lymphoma conditions and between chemotherapy cytotoxicity and aggravation of the immune system and associated hematopoietic dysfunction, considering the role of all these components in light of the initially undiagnosed cartilage hair hypoplasia. Finally, this case highlights the importance of screening for primary immunodeficiencies in the setting of a diagnosis of lymphoma and/or dwarfism; moreover, CHH must be distinguished from other causes of small size; its diagnosis and complete check-up must include the molecular characterisation, and its management must be global in collaboration with haematologists, immunologists and internists.


Assuntos
Síndrome de Imunodeficiência Adquirida/diagnóstico , Cartilagem/anormalidades , Tratamento Farmacológico , Cabelo/anormalidades , Doença de Hirschsprung/diagnóstico , Síndromes de Imunodeficiência/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Osteocondrodisplasias/congênito , Adulto , Nanismo , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hirschsprung/genética , Humanos , Síndromes de Imunodeficiência/genética , Linfoma Difuso de Grandes Células B/complicações , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Suíça
16.
J Pediatr Adolesc Gynecol ; 31(4): 422-425, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29462708

RESUMO

BACKGROUND: Cartilage-hair hypoplasia (CHH) is a rare chondrodysplasia, including disproportionate short stature, hypoplastic hair, immunodeficiency, and increased risk of malignancies. Absent pubertal growth spurt and absent pubic hair complicate monitoring of pubertal development in these patients. CASES: Two CHH patients with delayed puberty and excessive growth failure are described. One of the girls had hypogonadotropic hypogonadism whereas the other had hyponormogonadotropic hypogonadism with no spontaneous pubertal development and slow response to estrogen therapy, both requiring permanent replacement therapy. SUMMARY AND CONCLUSION: Careful follow-up of pubertal development in individuals with CHH and other growth-restricting bone diseases is needed. In delayed pubertal development timely hormone therapy is essential to ensure maximal growth and well developed secondary sex characteristics.


Assuntos
Cabelo/anormalidades , Doença de Hirschsprung/complicações , Terapia de Reposição Hormonal/métodos , Hipogonadismo/etiologia , Síndromes de Imunodeficiência/complicações , Osteocondrodisplasias/congênito , Puberdade Tardia/etiologia , Adolescente , Criança , Feminino , Doença de Hirschsprung/tratamento farmacológico , Humanos , Hipogonadismo/tratamento farmacológico , Síndromes de Imunodeficiência/tratamento farmacológico , Osteocondrodisplasias/complicações , Osteocondrodisplasias/tratamento farmacológico , Puberdade Tardia/tratamento farmacológico , Estudos Retrospectivos , Adulto Jovem
17.
J Dermatol ; 45(5): 613-617, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29464811

RESUMO

Autosomal recessive woolly hair is a relatively rare hereditary hair disorder characterized by sparse, short, curly hair. This condition is known to be caused by mutations in the LIPH gene, LPAR6 gene or KRT25 gene. In the Japanese population, most patients with autosomal recessive woolly hair carry one of two founder mutations in the LIPH gene, c.736T>A (p.Cys246Ser) or c.742C>A (p.His248Asn). However, occasionally, individuals with this condition carry compound heterozygous mutations, typically one founder mutation and another mutation. In this study, we describe a patient with a compound heterozygous mutation in the LIPH gene at c.736T>A and c.1095-3C>G. The latter mutation created a novel splice site. This was the fourth splice site mutation to be described in the LIPH gene. Furthermore, we performed an in vitro transcription assay in cultured cells, and demonstrated that the c.1095-3C>G mutation led to a frame-shift, which created a premature termination codon at the protein level (p.Glu366Ilefs*7). Finally, we summarized the mutations previously reported for the LIPH gene. Our findings provide further clues as to the molecular basis of autosomal recessive woolly hair.


Assuntos
Doenças do Cabelo/genética , Cabelo/anormalidades , Hipotricose/genética , Lipase/genética , Sítios de Splice de RNA/genética , Pré-Escolar , Códon sem Sentido , Análise Mutacional de DNA , Mutação da Fase de Leitura , Heterozigoto , Humanos , Masculino
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