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.

A systematic review of genetic syndromes with obesity

“…A re‐examination of this region by Milunsky et al confirmed that the original study published was a false positive . A homozygous balanced reciprocal translocation (16;20)(q21;p11.2) suggested LINC00237 to be a candidate gene for MOMO syndrome . However, due to the lack of a confirmatory study, this finding could not be verified, and the genetic aetiology of MOMO syndrome is still debated.…”

Loss of renal SNX5 results in impaired IDE activity and insulin resistance in mice

“…Furthermore, studies on the role of SNX5 in energy metabolism could indicate a yet undescribed role in the aetiology of metabolic syndrome, since hypertension and insulin resistance are cornerstones of the syndrome. The human SNX5 gene maps at 20p11.23, a locus that has been implicated in the aetiology of the MOMO (macrosomia, obesity, macrocephaly and ocular abnormalities) syndrome [46], which includes obesity, another hallmark of the metabolic syndrome [47]. …”

LncRNA ZNF503-AS1 promotes RPE differentiation by downregulating ZNF503 expression

“… 19 Roles of lncRNAs in ocular diseases, such as diabetic retinopathy, proliferative vitreoretinopathy, glaucoma, ocular tumors, and ocular neovascularization, have also been identified. 11 , 14 , 20 , 21 , 22 , 23 , 24 , 25 , 26 However, the association between lncRNAs and RPE differentiation is poorly understood. In this study, we aim to reveal the roles of a lncRNA, ZNF503-AS1 , in RPE differentiation, and to seek for a lncRNA-based potential therapeutic target for dry AMD.…”