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Molecular and clinical studies in 107 Noonan syndrome affected individuals with PTPN11 mutations.
Athota, Jeevana Praharsha; Bhat, Meenakshi; Nampoothiri, Sheela; Gowrishankar, Kalpana; Narayanachar, Sanjeeva Ghanti; Puttamallesh, Vinuth; Farooque, Mohammed Oomer; Shetty, Swathi.
Afiliação
  • Athota JP; Molecular Genetics, Centre for Human Genetics, Bengaluru, 560100, India.
  • Bhat M; Molecular Genetics, Centre for Human Genetics, Bengaluru, 560100, India.
  • Nampoothiri S; Pediatric Genetics, Indira Gandhi Institute of Child Health, Bengaluru, 560029, India.
  • Gowrishankar K; Pediatric Genetics, Amrita Institute of Medical Sciences & Research Centre (AIMS), Kochi, 682041, India.
  • Narayanachar SG; Medical Genetics, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, 600034, India.
  • Puttamallesh V; Pediatric Genetics, Indira Gandhi Institute of Child Health, Bengaluru, 560029, India.
  • Farooque MO; Molecular Genetics, Centre for Human Genetics, Bengaluru, 560100, India.
  • Shetty S; Molecular Genetics, Centre for Human Genetics, Bengaluru, 560100, India.
BMC Med Genet ; 21(1): 50, 2020 03 12.
Article em En | MEDLINE | ID: mdl-32164556
BACKGROUND: Noonan syndrome (NS), an autosomal dominant developmental genetic disorder, is caused by germline mutations in genes associated with the RAS / mitogen-activated protein kinase (MAPK) pathway. In several studies PTPN11 is one of the genes with a significant number of pathogenic variants in NS-affected patients. Therefore, clinically diagnosed NS individuals are initially tested for pathogenic variants in PTPN11 gene to confirm the relationship before studying genotype-phenotype correlation. METHODS: Individuals (363) with clinically diagnosed NS from four hospitals in South India were recruited and the exons of PTPN11 gene were sequenced. RESULTS: Thirty-two previously described pathogenic variants in eight different exons in PTPN11 gene were detected in 107 patients, of whom 10 were familial cases. Exons 3, 8 and 13 had the highest number of pathogenic variants. The most commonly identified pathogenic variants in this series were in exon 8 (c.922A > G, c.923A > G), observed in 22 of the affected. Congenital cardiac anomalies were present in 84% of the mutation-positive cohort, the majority being defects in the right side of the heart. The most common facial features were downward-slanting palpebral fissures, hypertelorism and low-set posteriorly rotated ears. Other clinical features included short stature (40%), pectus excavatum (54%) and, in males, unilateral or bilateral cryptorchidism (44%). CONCLUSION: The clinical features and mutational spectrum observed in our cohort are similar to those reported in other large studies done worldwide. This is the largest case series of NS-affected individuals with PTPN11 mutations described till date from India.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polimorfismo de Nucleotídeo Único / Proteína Tirosina Fosfatase não Receptora Tipo 11 / Síndrome de Noonan Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Newborn País/Região como assunto: Asia Idioma: En Revista: BMC Med Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Índia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polimorfismo de Nucleotídeo Único / Proteína Tirosina Fosfatase não Receptora Tipo 11 / Síndrome de Noonan Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Newborn País/Região como assunto: Asia Idioma: En Revista: BMC Med Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Índia