Deletion 1q43-44 in a patient with clinical diagnosis of Warburg-Micro syndrome

Am J Med Genet A. 2015 Jun;167(6):1243-51. doi: 10.1002/ajmg.a.36878. Epub 2015 Apr 21.


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.

Keywords: Del 1q43-q44; WARBM; Warburg-Micro syndrome; genes related with vesicular transport.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics
  • Adolescent
  • Cataract / congenital*
  • Cataract / diagnosis
  • Cataract / genetics
  • Cataract / pathology
  • Chromosome Deletion
  • Chromosomes, Human, Pair 1 / genetics
  • Comparative Genomic Hybridization
  • Cornea / abnormalities*
  • Cornea / pathology
  • Cytokines
  • DNA Mutational Analysis
  • Exons
  • Formins
  • Genetic Association Studies
  • Haploinsufficiency*
  • Humans
  • Hypogonadism / diagnosis
  • Hypogonadism / genetics*
  • Hypogonadism / pathology
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Intercellular Signaling Peptides and Proteins / deficiency
  • Intercellular Signaling Peptides and Proteins / genetics
  • Male
  • Microcephaly / diagnosis
  • Microcephaly / genetics*
  • Microcephaly / pathology
  • Microfilament Proteins / deficiency
  • Microfilament Proteins / genetics
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Optic Atrophy / diagnosis
  • Optic Atrophy / genetics*
  • Optic Atrophy / pathology
  • RGS Proteins / deficiency
  • RGS Proteins / genetics
  • Receptor, Muscarinic M3
  • Receptors, Muscarinic / deficiency
  • Receptors, Muscarinic / genetics
  • Rod Opsins / deficiency
  • Rod Opsins / genetics


  • Adaptor Proteins, Signal Transducing
  • CHML protein, human
  • CHRM3 protein, human
  • Cytokines
  • Fmn2 protein, human
  • Formins
  • GREM2 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • Nuclear Proteins
  • OPN3 protein, human
  • RGS Proteins
  • RGS7 protein, human
  • Receptor, Muscarinic M3
  • Receptors, Muscarinic
  • Rod Opsins

Supplementary concepts

  • Chromosome 1q43-Q44 Deletion Syndrome
  • Warburg Sjo Fledelius syndrome