RESUMEN
NR4A2, a member of the nuclear receptor superfamily, is involved in modulation of target gene transcription, regulating several developmental processes such as regulation of cellular homeostasis, neuronal development, inflammation and carcinogenesis. 2q24.1 deletions are extremely rare, and only 1 patient with a de novo deletion encompassing only NR4A2 gene was reported so far. We report 3 additional patients with a de novo deletion encompassing NR4A2: 2 patients have deletions encompassing only NR4A2 gene and 1 patient has a deletion including NR4A2 and the first exon of GPD2. Our patients presented a neurodevelopmental disorder including language impairment, developmental delay, intellectual disability and/or autism spectrum disorder. We suggest that NR4A2 haploinsufficiency is implicated in neurodevelopmental disorder with high penetrance.
Asunto(s)
Trastorno del Espectro Autista/genética , Glicerolfosfato Deshidrogenasa/genética , Discapacidad Intelectual/genética , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Adolescente , Trastorno del Espectro Autista/fisiopatología , Niño , Exones/genética , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haploinsuficiencia/genética , Humanos , Discapacidad Intelectual/fisiopatología , MasculinoRESUMEN
Oral-facial-digital (OFD) syndromes are a subgroup of ciliopathies distinguished by the co-occurrence of hamartomas and/or multiple frenula of the oral region and digital anomalies. Several clinical forms of OFD syndromes are distinguished by their associated anomalies and/or inheritance patterns, and at least 20 genetic types of OFD syndromes have been delineated. We describe here a child with preaxial and postaxial polydactyly, lingual hamartoma, a congenital heart defect, delayed development and cerebellar peduncles displaying the molar tooth sign. Whole-exome sequencing and SNP array identified compound heterozygous variants in the INTU gene, which encodes a protein involved in the positioning of the ciliary basal body. INTU is a subunit of the CPLANE multiprotein complex essential for the assembly of IFT-A particles and intraflagellar transport. This report of a second patient with INTU-related OFD syndrome and the further delineation of its neuroimaging and skeletal phenotype now allow INTU-related OFD syndromes to be classified within the OFD syndrome type VI group. Patients display a phenotype similar to that of mice with a hypomorphic mutation of Intu, but with the addition of a heart defect.
Asunto(s)
Proteínas del Citoesqueleto/genética , Proteínas de la Membrana/genética , Síndromes Orofaciodigitales/genética , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Síndromes Orofaciodigitales/diagnóstico por imagenRESUMEN
Heteromorphism or chromosomal variants are usually attributed to structural variations in constitutive heterochromatin. In the case of chromosome 18, 25 cases of 18ph+ have been reported to date. Using the Primed In Situ Labelling technique (PRINS) to study 2 new cases of 18ph+, we have been able to confirm their molecular nature and assuming a mechanism of formation. Although such chromosomal variants are usually thought to have no adverse clinical consequence, a review of the literature shows that many cases were diagnosed because of recurrent abortion, malformed or mentally retarded children suggesting the possible relationship between 18ph+ and such clinical outcomes.