Clinical report of a pure subtelomeric 1qter deletion in a boy with mental retardation and multiple anomalies adds further evidence for a specific phenotype

Abstract

Deletions of the 1q telomere have been reported in several studies screening for subtelomeric rearrangements. However, an adequate clinical description is available from only a few patients. We provide a clinical description of a patient with a subtelomeric deletion of chromosome 1q, previously detected by us in a screening study. Comparison of the clinical presentation of our patient with rare cases reported previously provides further evidence for a specific phenotype of 1q patients, including mental retardation, growth retardation, sometimes with prenatal onset, progressive microcephaly, seizures, hand and foot abnormalities and a variety of midline defects, including corpus callosum, cardiac, genital and gastro-esophageal abnormalities. This clinical presentation is reminiscent of that of patients with larger, microscopically visible deletions of chromosome 1q (>3 Mb) characterized by growth and mental retardation, coarse faces with thin upper lip, epilepsy, and variable other anomalies. In addition, the breakpoint region was mapped to a 26 kb region within the RGS7 gene. Among the 17 known genes in the candidate region, are zinc-finger genes. Other members of this gene family have been implicated in different forms of mental retardation.

Subtelomeric deletions of 1q43q44 and severe brain impairment associated with delayed myelination

“…4,6,7,9,11,18 After chromosomal microarray testing has been available for the identification of submicroscopic chromosomal aberrations, many patients with submicroscopic deletions of 1q44 have been identified. 8,10,12,14,15 Now, precise genotype-phenotype correlation has been evaluated through the accumulation of patients with variable deletion sizes, and a minimal essential region has been proposed for expressing the main characteristics of 1q44 deletion syndrome.…”

“…3 Several studies have investigated the critical region for 1q44 subtelomeric deletion syndrome and found that the core phenotypic features of 1q44 subtelomeric deletion syndrome are microcephaly, abnormalities of the corpus callosum (ACC) and seizures. [4][5][6][7][8][9][10][11][12][13][14][15][16] Recently, Ballif et al 17 analyzed patients with microdeletions of 1q44 and proposed certain genes that may be responsible for individual features.…”

A de novo non-sense mutation in ZBTB18 in a patient with features of the 1q43q44 microdeletion syndrome

“…[1][2][3][4][5][6][7][8] Even for patients with an overlapping deletion, the phenotype varies considerably. So far, no direct association has been identified between the phenotype and the deleted genes.…”

“…1, 3,[8][9][10][11][12][13][14] Specifically, ZBTB18 has repeatedly been identified as a strong candidate gene for microcephaly and/or ACC. 7,9,11,14,15 ZBTB18 is particularly compelling since a brain-specific knock-out of this gene in mice causes microcephaly and callosal anomalies. 16 However, other studies suggest critical regions that do not include ZBTB18.…”

Prenatal Diagnosis of a Fetus with Terminal Deletion of Chromosome 1 (q43) in First-Trimester Screening: Is There a Characteristic Antenatal 1q Deletion Phenotype? A Case Report and Review of the Literature

“…The most frequently associated features include short stature, microcephaly with developmental delay and mental retardation, seizures, abnormal corpus callosum and abnormal ears [5][6][7][8] . Still, one has to be aware that there is a benign variant: deletions smaller than 2 Mbp seem to have no clinical consequences, as shown by Roos et al [9] .…”