title: Deletion 1q43-44 in a patient with clinical diagnosis of Warburg-Micro syndrome.
abstract: Warburg-Micro syndrome (WARBM) is an autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy and central nervous system malformations. This syndrome is caused by mutations in the RAB3GAP1/2 and RAB18 genes, part of the Rab family, and in the TBC1D20 gene, which contributes to lipid droplet formation/metabolism. Here we present a patient with clinical diagnosis of WARBM syndrome, who did not have mutations in either the RAB3GAP1/2 genes, in the main exons of RAB18, nor in the TBC1D20 gene. However, the analysis with CGH-array detected a 9.6 Mb deletion at 1q43-qter. We performed a genotype-phenotype correlation using 20 previously published patients in whom the coordinates of the deleted regions were defined. The comparative analysis revealed that the current patient and three of the other 20 patients share the loss of six genes, four of which are related with the family of G proteins, and are strongly expressed in the brain, retina, heart and kidney. Consequently, their haploinsufficiency may result in different combinations of clinical alterations, including some of those of WARBM syndrome. In addition, the haploinsufficiency of other genes may contribute to other defects and clinical variability. Additionally, for the genotype-phenotype correlation, one must also consider molecular pathways that can result in the observed alterations. To early confirm a genetic diagnosis is essential for the patient and family. The current patient was considered as having a recessive syndrome, but since he had a "de novo" deletion, there was not an increased recurrence risk.
authors.affiliation: Servicio de Pediatría, Hospital San Pedro de Alcántara, Cáceres, Spain.|Spanish Collaborative Study of Congenital Malformations (ECEMC), Spain.|CIBER de Enfermedades Raras (CIBERER) (U724), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Arroyo-Carrera
authors.affiliation: Servicio de Pediatría, Hospital San Pedro de Alcántara, Cáceres, Spain.|Spanish Collaborative Study of Congenital Malformations (ECEMC), Spain.
authors.forename: María Solo
authors.initials: MS
authors.lastname: de Zaldívar Tristancho
authors.affiliation: Spanish Collaborative Study of Congenital Malformations (ECEMC), Spain.|CIBER de Enfermedades Raras (CIBERER) (U724), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain.|Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud Carlos III, Madrid, Spain.|Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Bermejo-Sánchez
authors.affiliation: Spanish Collaborative Study of Congenital Malformations (ECEMC), Spain.|CIBER de Enfermedades Raras (CIBERER) (U724), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain.|Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martínez-Fernández
authors.affiliation: Servicio de Neuropediatría, Hospital San Pedro de Alcántara, Cáceres, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: López-Lafuente
authors.affiliation: Spanish Collaborative Study of Congenital Malformations (ECEMC), Spain.|Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: MacDonald
authors.affiliation: Servicio de Genética y Biología Molecular, Hospital Universitario de la Ribera, Alzira, Valencia, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Zúñiga
authors.affiliation: Centro Andaluz de Biología del Desarrollo, CSIC/Universidad Pablo de Olavide, Sevilla, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Luis Gómez-Skarmeta
authors.affiliation: Spanish Collaborative Study of Congenital Malformations (ECEMC), Spain.|CIBER de Enfermedades Raras (CIBERER) (U724), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain.|Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud Carlos III, Madrid, Spain.|Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Luisa Martínez-Frías
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics; D000293:Adolescent; D002386:Cataract / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D003315:Cornea / Q000002:abnormalities* / Q000473:pathology; D016207:Cytokines; D004252:DNA Mutational Analysis; D005091:Exons; D000080865:Formins; D056726:Genetic Association Studies; D057895:Haploinsufficiency; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics; D008297:Male; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics; D009896:Optic Atrophy / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020710:RGS Proteins / Q000172:deficiency / Q000235:genetics; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000172:deficiency / Q000235:genetics; D017299:Rod Opsins / Q000172:deficiency / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C085460:CHML protein, human; C000595896:CHRM3 protein, human; D016207:Cytokines; C587953:Fmn2 protein, human; D000080865:Formins; C495107:GREM2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; C430099:OPN3 protein, human; D020710:RGS Proteins; C492039:RGS7 protein, human; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D017299:Rod Opsins
keywords: Del 1q43-q44; WARBM; Warburg-Micro syndrome; genes related with vesicular transport