RESUMO
We here describe novel compound heterozygous missense variants, NM_133443:c.[400C>T] and NM_133443:[1435G>A], in the glutamic-pyruvic transaminase 2 (GPT2) gene in a large consanguineous family with two affected siblings diagnosed with microcephaly intellectual disability and developmental delay (IDD). In addition to these clinical phenotypes, the male sibling has spastic paraplegia, and the female sibling has epilepsy. Their four extended family members have IDD and microcephaly. Both of these variants, c.400C>T (p.R134C) and c.1435G>A (p.V479M), reside in the pyridoxal phosphate-dependent aminotransferase domain. The missense variants affect highly conserved amino acids and are classified to be disease-causing by meta-SVM. The candidate variants were not found in the Exome Aggregation Consortium (ExAC) dataset or in dbSNP. Both GPT2 variants have an allele frequency of 0% (0/ â¼ 600) in the whole-exome sequenced Turkish cohort. Upon Sanger sequencing, we confirmed these mutations in all affected family members and showed that the index patient and his affected sister inherited one mutant allele from each unaffected parent. To the best of our knowledge, this is the first family in which a novel compound heterozygous variant in the GPT2 gene was identified.
Assuntos
Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Microcefalia/genética , Transaminases/genética , Adolescente , Criança , Pré-Escolar , Consanguinidade , Deficiências do Desenvolvimento/fisiopatologia , Epilepsia/genética , Epilepsia/fisiopatologia , Exoma/genética , Feminino , Heterozigoto , Humanos , Deficiência Intelectual/fisiopatologia , Masculino , Microcefalia/fisiopatologia , Pessoa de Meia-Idade , Mutação , Paraplegia/genética , Paraplegia/fisiopatologia , Linhagem , Fenótipo , Irmãos , Sequenciamento do ExomaRESUMO
We present a novel technique for three-dimensional (3D) image processing of complex fields. It consists in inverting the coherent image formation by filtering the complex spectrum with a realistic 3D coherent transfer function (CTF) of a high-NA digital holographic microscope. By combining scattering theory and signal processing, the method is demonstrated to yield the reconstruction of a scattering object field. Experimental reconstructions in phase and amplitude are presented under non-design imaging conditions. The suggested technique is best suited for an implementation in high-resolution diffraction tomography based on sample or illumination rotation.