title: Subtelomeric 6p25 deletion/duplication: Report of a patient with new clinical findings and genotype-phenotype correlations.
abstract: The 6p terminal deletions are rare and present variability of clinical features, which increases the importance of reporting additional cases in order to better characterize genotype-phenotype correlations. We report a 12-year-old girl with a de novo deletion in 6p25.1-pter characterized by high-resolution karyotyping and FISH. Further analysis using oligonucleotide array-CGH revealed a 5.06 Mb 6p25.1-pter deletion associated with a contiguous 1 Mb 6p25.1 duplication. The patient presented normal growth, developmental delay, frontal bossing, severe hypertelorism, corectopia, wide and depressed nasal bridge, mild learning disability, hearing loss and diffuse leukopathy. Additionaly, she presented peculiar phenotypic features reported herein for the first time in 6p25 deletion syndrome: cerebrospinal fluid fistula and bones resembling those seen in 3-M syndrome. The distinctive phenotype of the 6p25 deletion syndrome has been mainly correlated with the FOXC1 and FOXF2 genes deletions, both related mainly to eye development. We also consider the SERPINB6 as a candidate for sensorineural hearing loss and TUBB2A as a candidate for our patient's skeletal features. In addition, as our patient had a duplication including NRN1, a gene related with neurodevelopment, synaptic plasticity and cognitive dysfunction in schizophrenia, we suggest that this gene could be associated with her white matter abnormalities and neurocognitive phenotype.
authors: Setor de Citogenética/Laboratório Central do Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address: nataliaduarte@ufmg.br.
authors: Natália D
authors: ND
authors: Linhares
authors: Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Marta
authors: M
authors: Svartman
authors: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors: Tatiane C
authors: TC
authors: Rodrigues
authors: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors: Carla
authors: C
authors: Rosenberg
authors: Departamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Eugênia R
authors: ER
authors: Valadares
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging* / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D058674:Chromosome Duplication; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D009479:Neuropeptides / Q000235:genetics; D011859:Radiography; D015843:Serpins / Q000235:genetics; D014404:Tubulin / Q000235:genetics
chemical_list: C112743:FOXC1 protein, human; C486413:FOXF2 protein, human; D051858:Forkhead Transcription Factors; D058851:GPI-Linked Proteins; C484539:NRN1 protein, human; D009479:Neuropeptides; D015843:Serpins; D014404:Tubulin; C094472:serpin B6
keywords: 6p deletion; Comparative genomic hybridization; Human FOXC1 protein; Human FOXF2 protein; Human NRN1 protein; Human SERPINB6 protein; Human TUBB2A protein