RESUMO
Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder frequently linked to n.72A>G (previously known as n.70A>G and n.71A>G), the most common RMRP variant worldwide. More than 130 pathogenic variants in this gene have already been described associated with CHH, and founder alterations were reported in the Finnish and Japanese populations. Our previous study in Brazilian CHH patients showed a high prevalence of n.197C>T variant (former n.195C>T and n.196C>T) when compared to other populations. The aim of this study was to investigate a possible founder effect of the n.197C>T variant in the RMRP gene in a series of CHH Brazilian patients. We have selected four TAG SNPs within chromosome 9 and genotyped the probands and their parents (23 patients previously described and nine novel). A common haplotype to the n.197C>T variant carriers was identified. Patients were also characterized for 46 autosomal Ancestry Informative Markers (AIMs). European ancestry was the most prevalent (58%), followed by African (24%) and Native American (18%). Our results strengthen the hypothesis of a founder effect for the n.197C>T variant in Brazil and indicate that this variant in the RMRP gene originated from a single event on chromosome 9 with a possible European origin.
Assuntos
Efeito Fundador , Cabelo , Doença de Hirschsprung , Osteocondrodisplasias , Polimorfismo de Nucleotídeo Único , Humanos , Brasil , Doença de Hirschsprung/genética , Masculino , Osteocondrodisplasias/genética , Osteocondrodisplasias/congênito , Feminino , Cabelo/anormalidades , RNA Longo não Codificante/genética , Haplótipos , Doenças da Imunodeficiência Primária/genética , Hipotricose/genética , Cromossomos Humanos Par 9/genética , CriançaRESUMO
Nicolaides-Baraitser Syndrome is a rare genetic condition that clinically presents with intellectual disabilities, facial and bone changes, and sparse hair. In Brazil, only one case has been previously reported without genetic confirmation. We present the case of an 8-year-old boy, clinically and genetically diagnosed with Nicolaides-Baraitser Syndrome, who developed autism spectrum disorder characteristics with a formal diagnosis at the age of eight. Diagnosing autism spectrum disorder in patients with intellectual disabilities is a clinical challenge requiring careful evaluation.
Assuntos
Transtorno do Espectro Autista , Hipotricose , Deficiência Intelectual , Masculino , Humanos , Criança , Deficiência Intelectual/complicações , Deficiência Intelectual/diagnóstico , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/diagnóstico , Hipotricose/complicações , Hipotricose/diagnóstico , Hipotricose/genética , FáciesAssuntos
Caderinas/genética , Hipotricose/genética , Degeneração Macular/genética , Doença de Stargardt/genética , Brasil/epidemiologia , Exoma/genética , Feminino , Predisposição Genética para Doença , Humanos , Hipotricose/epidemiologia , Hipotricose/patologia , Degeneração Macular/epidemiologia , Degeneração Macular/patologia , Masculino , Mutação/genética , Linhagem , Doença de Stargardt/epidemiologia , Doença de Stargardt/patologia , Sequenciamento do ExomaRESUMO
Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by sparse scalp hair caused by hair follicle abnormalities as well as progressive retinal degeneration leading to blindness in the second or third decade of life. It is associated with mutations of the cadherin 3 (CDH3) gene, which result in abnormal expression of P-cadherin. Mutations in CDH3 are related to ectodermal dysplasia, ectrodactyly, and macular dystrophy. In this report, we describe an 11-year-old Iranian boy born with a missing left index fingernail and sparse scalp hair who later displayed macular pigmentary changes. Genetic testing of the CDH3 gene revealed a homozygous gene variant at exon 6 (640A>T). This novel in-frame mutation converts a lysine to a premature stop codon, altering synthesis of P-cadherin on chromosome 16q22.
Assuntos
Caderinas/genética , Distrofias Hereditárias da Córnea/genética , Hipotricose/genética , Degeneração Macular/genética , Criança , Humanos , Irã (Geográfico) , Masculino , MutaçãoRESUMO
ABSTRACT Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by sparse scalp hair caused by hair follicle abnormalities as well as progressive retinal degeneration leading to blindness in the second or third decade of life. It is associated with mutations of the cadherin 3 (CDH3) gene, which result in abnormal expression of P-cadherin. Mutations in CDH3 are related to ectodermal dysplasia, ectrodactyly, and macular dystrophy. In this report, we describe an 11-year-old Iranian boy born with a missing left index fingernail and sparse scalp hair who later displayed macular pigmentary changes. Genetic testing of the CDH3 gene revealed a homozygous gene variant at exon 6 (640A>T). This novel in-frame mutation converts a lysine to a premature stop codon, altering synthesis of P-cadherin on chromosome 16q22.
RESUMO Hipotricose com distrofia macular juvenil (HDMJ) é uma doença autossômica recessiva rara caracterizada por rarefação capilar por alteração nos folículos pilosos e degeneracão progressiva da retina levando a cegueira na segunda e terceira década de vida. Associada a mutações no gene CDH3, resultando em expressão anormal de P-caderina. Mutações no gene CDH3 estão relacionados à displasia ectodérmica, ectrodactilia e distrofia macular. Neste relato descrevemos um menino Iraniano de 11 anos de idade, com ausência da unha na mão esquerda e rarefação capilar desde o nascimento, e que posteriormente apresentou alterações pigmentares maculares. Teste genético do gene CDH3 revelou uma variação homozigótica no exon 6 (640A>T). Essa mutação in-frame troca uma lisina por um codon de parada prematura, alterando a síntese da proteína P-caderina no cromossomo 16q22.
Assuntos
Humanos , Masculino , Criança , Caderinas/genética , Distrofias Hereditárias da Córnea/genética , Hipotricose/genética , Degeneração Macular/genética , Irã (Geográfico) , MutaçãoRESUMO
Mutations in the EDA gene are responsible for X-linked hypohidrotic ectodermal dysplasia, the most common form of ectodermal dysplasia. Males show a severe form of this disease, while females often manifest mild to moderate symptoms. We identified a missense mutation (c.463C>T) in the EDA gene in a Jordanian family, using direct DNA sequencing. This mutation leads to an amino acid change of arginine to cysteine in the extracellular domain of ectodysplasin-A, a protein encoded by the EDA gene. The phenotype of a severely affected 11-year-old boy with this mutation included heat intolerance, sparse hair (hypotrichosis), absence of 17 teeth (oligodontia), speech problems, and damaged eccrine glands, resulting in reduced sweating (anhidrosis). Both the mother (40 years old) and the sister (10 years old) were carriers with mild to moderate symptoms of this disease, while the father was healthy. This detailed description of the phenotype caused by this missense mutation could be useful for prenatal diagnosis.
Assuntos
Displasia Ectodérmica Anidrótica Tipo 1/genética , Ectodisplasinas/genética , Mutação de Sentido Incorreto , Distúrbios da Fala/genética , Adulto , Criança , Glândulas Écrinas/anormalidades , Saúde da Família , Feminino , Humanos , Hipo-Hidrose/genética , Hipotricose/genética , Jordânia , Masculino , Análise de Sequência de DNA , Anormalidades Dentárias/genéticaRESUMO
While there have been significant advances in understanding the genetic etiology of human hair loss over the previous decade, there remain a number of hereditary disorders for which a causative gene has yet to be identified. We studied a large, consanguineous Brazilian family that presented with woolly hair at birth that progressed to severe hypotrichosis by the age of 5, in which 6 of the 14 offspring were affected. After exclusion of known candidate genes, a genome-wide scan was performed to identify the disease locus. Autozygosity mapping revealed a highly significant region of extended homozygosity (lod score of 10.41) that contained a haplotype with a linkage lod score of 3.28. Results of these two methods defined a 9-Mb region on chromosome 13q14.11-q14.2. The interval contains the P2RY5 gene, in which we recently identified pathogenic mutations in several families of Pakistani origin affected with autosomal recessive woolly and sparse hair. After the exclusion of several other candidate genes, we sequenced the P2RY5 gene and identified a homozygous mutation (C278Y) in all affected individuals in this family. Our findings show that mutations in P2RY5 display variable expressivity, underlying both hypotrichosis and woolly hair, and underscore the essential role of P2RY5 in the tissue integrity and maintenance of the hair follicle.
Assuntos
Genes Recessivos , Predisposição Genética para Doença , Hipotricose/genética , Mutação , Receptores Purinérgicos P2/genética , Sequência de Aminoácidos , Animais , Brasil , Mapeamento Cromossômico , Cromossomos Humanos Par 13/genética , Feminino , Ligação Genética , Humanos , Escore Lod , Masculino , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Linhagem , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNARESUMO
Bazex-Dupré-Christol syndrome is a rare genodermatosis with cancer predisposition, characterized by follicular atrophoderma, multiple milia, congenital hypotrichosis, hypohidrosis and basal cell malformations that include nevoid basal cell carcinomas of early onset. We present two patients with this syndrome, a 1-year-old boy with diffuse scalp and eyebrows alopecia, milia papules on the face, ears, trunk, and limbs. Hypohidrosis was observed on his trunk and head. His 16-year-old mother had identical changes since childhood, with hair fragility, and multiple atrophic "ice pick" follicular depressions on the dorsa of her hands. She also had a basal cell carcinoma on her face. Microscopic examination of hairs from the mother revealed abnormalities such as diameter irregularities, broken shafts, trichorrexis nodosa and pili bifurcatti. Pili bifurcatti is an uncommon hair shaft dysplasia that has not before been observed in Bazex-Dupré-Christol syndrome.
Assuntos
Síndrome do Nevo Basocelular/genética , Carcinoma Basocelular/patologia , Heterozigoto , Lesões Pré-Cancerosas/patologia , Neoplasias Cutâneas/genética , Acrodermatite/diagnóstico , Acrodermatite/genética , Adolescente , Síndrome do Nevo Basocelular/diagnóstico , Carcinoma Basocelular/diagnóstico , Transformação Celular Neoplásica , Feminino , Humanos , Hipo-Hidrose/diagnóstico , Hipo-Hidrose/genética , Hipotricose/diagnóstico , Hipotricose/genética , Lactente , Masculino , Mães , Linhagem , Prognóstico , Neoplasias Cutâneas/diagnóstico , SíndromeRESUMO
Congenital hypotrichosis in mammalian species consists of partial or complete absence of hair at birth. The hairless gene is often responsible for this disorder in men, mice and rats. Recent experimental data on Valle del Belice sheep reared in Sicily for milk production, support the genetic control of the ovine hypotrichosis as a Mendelian recessive trait. The ovine hairless gene was chosen as the candidate gene involved in this disorder. Blood samples were collected from Valle del Belice sheep with the normal and hypotrichotic phenotypes. Almost the entire hairless gene was successfully amplified using the long PCR technique. Unrelated sheep with differing phenotypes were randomly chosen for sequencing the amplified products. Different mutations related to the hypotrichotic phenotype were found in exon 3. In fact, sequencing revealed an A/T transversion at position 739, a G/A transition at position 823, and a C/T transition at position 1312. From these nucleotide exchanges, three substitutions of the processed mature protein were deduced at the amino acid positions 247 (Thr/Ser), 275 (Ala/Thr), and 438 (Gln/Stop). A PCR-SSCP based test was developed in order to detect the last mutation, which is responsible for the hypotrichotic phenotype.