title: Haploinsufficiency of ANO6, NELL2 and DBX2 in a boy with intellectual disability and growth delay.
abstract: We report on a 10-year-old-boy presenting with moderate intellectual disability (ID), impaired motor skills, hypotonia, growth delay, minor anomalies, misaligned teeth, pectus excavatum, small hands and feet, widely spaced nipples, and a 1.13 Mb de novo deletion on HSA12q12 (chr12:44,830,147-45,964,945 bp, hg19), deleting ANO6, NELL2, and DBX2 and the pseudogenes PLEKHA8P1 and RACGAP1P. We suggest DBX2 and NELL2 as disease-causing genes and their haploinsufficiency to be involved in the psychomotor delay in the patient. DBX2 encodes a homeobox protein, highly expressed during neuronal development and regulating differentiation of interneurons in brain and spinal cord. NELL2 is expressed in most of the central and peripheral nervous system, with highest expression in hippocampus and cerebellum, maximizing during neuronal differentiation. The deletion in our patient is the smallest in HSA12q12 reported to date, and it is included in the deletion carried by four previously reported patients. The clinical presentation of these patients points to the recurrence of the following manifestation, possibly delineating a 12q12 deletion syndrome phenotype: moderate to severe developmental/intellectual delay, hypotonia, postnatal growth retardation, skeletal and dental anomalies, minor facial anomalies including strabismus, down slanting palpebral fissures, and large/low-set ears.
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Ellen Ø
authors.initials: EØ
authors.lastname: Carlsen
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Eirik
authors.initials: E
authors.lastname: Frengen
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Fannemel
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Doriana
authors.initials: D
authors.lastname: Misceo
mesh_terms: D000075368:Anoctamins; D002648:Child; D002658:Developmental Disabilities / Q000235:genetics*; D057895:Haploinsufficiency; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D049294:Phospholipid Transfer Proteins / Q000235:genetics*
chemical_list: C555078:ANO6 protein, human; D000075368:Anoctamins; C104145:NELL2 protein, human; D009419:Nerve Tissue Proteins; D049294:Phospholipid Transfer Proteins
keywords: 12q12 microdeletion syndrome; ANO6/TMEM16F; DBX2; NELL2; developmental disorder