RESUMO
OBJECTIVE: To analyze the lymphocyte subsets in individuals with Kabuki syndrome for better characterizing the immunological phenotype of this rare congenital disorder. METHODS: We characterized the immunological profile including B-, T- and natural killer-cell subsets in a series (N = 18) of individuals with Kabuki syndrome. RESULTS: All 18 individuals underwent genetic analysis: 15 had a variant in KMT2D and 3 a variant in KDM6A. Eleven of the 18 individuals (61%) had recurrent infections and 9 (50%) respiratory infections. Three (17%) had autoimmune diseases. On immunological analysis, 6 (33%) had CD4 T-cell lymphopenia, which was preferentially associated with the KMT2D truncating variant (5/9 individuals). Eight of 18 individuals (44%) had a humoral deficiency and eight (44%) had B lymphopenia. We found abnormal distributions of T-cell subsets, especially a frequent decrease in recent thymic emigrant CD4 + naive T-cell count in 13/16 individuals (81%). CONCLUSION: The immunological features of Kabuki syndrome showed variable immune disorders with CD4 + T-cell deficiency in one third of cases, which had not been previously reported. In particular, we found a reduction in recent thymic emigrant naïve CD4 + T-cell count in 13 of 16 individuals, representing a novel finding that had not previously been reported.
Assuntos
Anormalidades Múltiplas , Proteínas de Ligação a DNA , Face , Histona Desmetilases , Proteínas de Neoplasias , Doenças Vestibulares , Humanos , Doenças Vestibulares/genética , Doenças Vestibulares/imunologia , Face/anormalidades , Feminino , Masculino , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/imunologia , Criança , Proteínas de Ligação a DNA/genética , Adolescente , Histona Desmetilases/genética , Pré-Escolar , Adulto , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Adulto Jovem , Lactente , Linfopenia/imunologia , Linfopenia/genética , Fenótipo , Doenças Hematológicas/genética , Doenças Hematológicas/imunologia , Mutação , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , ImunofenotipagemRESUMO
Cutis laxa (CL) is a rare connective tissue disorder characterized by wrinkled, abundant and sagging skin, sometimes associated with systemic impairment. Biallelic alterations in latent transforming growth factor beta-binding protein 4 gene (LTBP4) cause autosomal recessive type 1C cutis laxa (ARCL1C, MIM #613177). The present report describes the case of a 17-months-old girl with cutis laxa together with a literature review of previous ARCL1C cases. Based on proband main clinical signs (cutis laxa and pulmonary emphysema), clinical exome sequencing (CES) was performed and showed a new nine base-pairs homozygous in-frame deletion in LTBP4 gene. RT-PCR and cDNA Sanger sequencing were performed in order to clarify its impact on RNA. This report demonstrates that a genetic alteration in the EGF-like 14 domain calcium-binding motif of LTBP4 gene is likely responsible for cutis laxa in our patient.