title: A homozygous balanced reciprocal translocation suggests LINC00237 as a candidate gene for MOMO (macrosomia, obesity, macrocephaly, and ocular abnormalities) syndrome.
abstract: Macrosomia, obesity, macrocephaly, and ocular abnormalities syndrome (MOMO syndrome) has been reported in only four patients to date. In these sporadic cases, no chromosomal or molecular abnormality has been identified thus far. Here, we report on the clinical, cytogenetic, and molecular findings in a child of healthy consanguineous parents suffering from MOMO syndrome. Conventional karyotyping revealed an inherited homozygous balanced reciprocal translocation (16;20)(q21;p11.2). Uniparental disomy testing showed bi-parental inheritance for both derivative chromosomes 16 and 20. The patient's oligonucleotide array-comparative genomic hybridization profile revealed no abnormality. From the homozygous balanced reciprocal translocation (16;20)(q21;p11.2), a positional cloning strategy, designed to narrow 16q21 and 20p11.2 breakpoints, revealed the disruption of a novel gene located at 20p11.23. This gene is now named LINC00237, according to the HUGO (Human Genome Organization) nomenclature. The gene apparently leads to the production of a non-coding RNA. We established that LINC00237 was expressed in lymphocytes of control individuals while normal transcripts were absent in lymphocytes of our MOMO patient. LINC00237 was not ubiquitously expressed in control tissues, but it was notably highly expressed in the brain. Our results suggested autosomal recessive inheritance of MOMO syndrome. LINC00237 could play a role in the pathogenesis of this syndrome and could provide new insights into hyperphagia-related obesity and intellectual disability.
authors.affiliation: Univ. Bordeaux, Maladies Rares: Génétique et Métabolisme, Bordeaux, France.
authors.forename: Phi Yen
authors.initials: PY
authors.lastname: Vu
authors.forename: Jérôme
authors.initials: J
authors.lastname: Toutain
authors.forename: David
authors.initials: D
authors.lastname: Cappellen
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Delrue
authors.forename: Hussein
authors.initials: H
authors.lastname: Daoud
authors.forename: Azza Abd
authors.initials: AA
authors.lastname: El Moneim
authors.forename: Pascal
authors.initials: P
authors.lastname: Barat
authors.forename: Orianne
authors.initials: O
authors.lastname: Montaubin
authors.forename: Françoise
authors.initials: F
authors.lastname: Bonnet
authors.forename: Zong Qi
authors.initials: ZQ
authors.lastname: Dai
authors.forename: Christophe
authors.initials: C
authors.lastname: Philippe
authors.forename: Cong Toai
authors.initials: CT
authors.lastname: Tran
authors.forename: Caroline
authors.initials: C
authors.lastname: Rooryck
authors.forename: Benoît
authors.initials: B
authors.lastname: Arveiler
authors.forename: Robert
authors.initials: R
authors.lastname: Saura
authors.forename: Sylvain
authors.initials: S
authors.lastname: Briault
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Laurence
authors.initials: L
authors.lastname: Taine
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D056905:Chromosome Breakpoints; D003103:Coloboma / Q000175:diagnosis / Q000235:genetics*; D005320:Fetal Macrosomia / Q000175:diagnosis / Q000235:genetics*; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006257:Head / Q000002:abnormalities; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D059785:Karyotype; D008297:Male; D058627:Megalencephaly / Q000175:diagnosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009765:Obesity / Q000175:diagnosis / Q000235:genetics*; D016366:Open Reading Frames; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: C581712:LINC00237 RNA, human; D062085:RNA, Long Noncoding