RESUMO
Anophthalmia and microphthalmia are the most severe malformations of the eye, referring to a congenital absence, and a reduced size of the eyeball respectively. More than 20 genes have been shown to be mutated in patients with syndromic and non-syndromic forms of anophthalmia-microphthalmia. In a recent study combining autozygome and exome analysis, a homozygous loss of function mutation in TENM3 (previously named ODZ3) was reported in two siblings with isolated bilateral colobomatous microphthalmia from a consanguineous Saudi family. Herein, we report a third patient (not related to the previously reported family) with bilateral colobomatous microphthalmia and developmental delay in whom genetic studies identified a homozygous TENM3 splicing mutation c.2968-2A>T (p.Val990Cysfs*13). This report supports the association of TENM3 mutations with colobomatous microphthalmia and expands the phenotypic spectrum associated with mutations in this gene. © 2016 Wiley Periodicals, Inc.
Assuntos
Encefalopatias Metabólicas Congênitas/genética , Coloboma/genética , Opacidade da Córnea/genética , Deficiências do Desenvolvimento/genética , Predisposição Genética para Doença , Deficiência Intelectual/genética , Proteínas de Membrana/genética , Microcefalia/genética , Microftalmia/genética , Proteínas do Tecido Nervoso/genética , Processamento Alternativo/genética , Encefalopatias Metabólicas Congênitas/fisiopatologia , Criança , Coloboma/fisiopatologia , Opacidade da Córnea/fisiopatologia , Deficiências do Desenvolvimento/fisiopatologia , Homozigoto , Humanos , Deficiência Intelectual/fisiopatologia , Masculino , Microcefalia/fisiopatologia , Microftalmia/fisiopatologia , MutaçãoRESUMO
MECP2 (methyl CpG binding protein 2) duplication causes syndromic intellectual disability. Patients often suffer from life-threatening infections, suggesting an additional immunodeficiency. We describe for the first time the detailed infectious and immunological phenotype of MECP2 duplication syndrome. 17/27 analyzed patients suffered from pneumonia, 5/27 from at least one episode of sepsis. Encapsulated bacteria (S.pneumoniae, H.influenzae) were frequently isolated. T-cell immunity showed no gross abnormalities in 14/14 patients and IFNy-secretion upon ConA-stimulation was not decreased in 6/7 patients. In 6/21 patients IgG2-deficiency was detected - in 4/21 patients accompanied by IgA-deficiency, 10/21 patients showed low antibody titers against pneumococci. Supra-normal IgG1-levels were detected in 11/21 patients and supra-normal IgG3-levels were seen in 8/21 patients - in 6 of the patients as combined elevation of IgG1 and IgG3. Three of the four patients with IgA/IgG2-deficiency developed multiple severe infections. Upon infections pronounced acute-phase responses were common: 7/10 patients showed CRP values above 200 mg/l. Our data for the first time show systematically that increased susceptibility to infections in MECP2 duplication syndrome is associated with IgA/IgG2-deficiency, low antibody titers against pneumococci and elevated acute-phase responses. So patients with MECP2 duplication syndrome and low IgA/IgG2 may benefit from prophylactic substitution of sIgA and IgG.