RESUMO
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.
Assuntos
Anormalidades Múltiplas/genética , Coloboma/genética , Macrossomia Fetal/genética , Predisposição Genética para Doença , Homozigoto , Deficiência Intelectual/genética , Megalencefalia/genética , Obesidade/genética , RNA Longo não Codificante/genética , Translocação Genética , Anormalidades Múltiplas/diagnóstico , Sequência de Aminoácidos , Sequência de Bases , Criança , Pontos de Quebra do Cromossomo , Coloboma/diagnóstico , Macrossomia Fetal/diagnóstico , Perfilação da Expressão Gênica , Cabeça/anormalidades , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/diagnóstico , Cariótipo , Masculino , Megalencefalia/diagnóstico , Dados de Sequência Molecular , Mutação , Obesidade/diagnóstico , Fases de Leitura Aberta , FenótipoRESUMO
We report an unusual chromosome 22q11 deletion associated with an apparent complementary ring chromosome in a phenotypically normal woman with a family medical history of 22q11 deletion. Using peripheral blood samples, conventional karyotyping, Fluorescence In Situ Hybridization (FISH) analysis on metaphase spreads and oligo array-based comparative genomic hybridization (oligo array-CGH) were performed. After conventional cytogenetic examination, the chromosome formula was as follows: 47,XX,+r(?)[16]/46,XX[6]. The FISH analysis revealed that this patient had a rearranged chromosome 22 with decreased centromeric fluorescence intensity and deletion of the 22q11.2 locus. She also had a supernumerary ring chromosome composed of an alpha-satellite centromere of 22 origin and 22q11.2 locus. The oligo array-CGH profile showed a deletion of approximately 4.18 Mb on chromosome 22 with a log 2 intensity ratio mean deviation of the deleted region of about -0.29. The 22q11 deletion associated with a complementary ring chromosome described in our patient could be consistent with a centromere misdivision mechanism, with one chromosomal break occurring in the alpha-satellite array and a second one in the 22q11 locus, a mechanism which has recently been referred to as the McClintock mechanism.