Phenotype and 244k array‐CGH characterization of chromosome 13q deletions: An update of the phenotypic map of 13q21.1‐qter

Abstract

Partial deletions of the long arm of chromosome 13 lead to variable phenotypes dependant on the size and position of the deleted region. In order to update the phenotypic map of chromosome 13q21.1-qter deletions, we applied 244k Agilent oligonucleotide-based array-CGH to determine the exact breakpoints in 14 patients with partial deletions of this region. Subsequently, we linked the genotype to the patient's phenotype. Using this approach, we were able to refine the smallest deletion region linked to short stature (13q31.3: 89.5-91.6 Mb), microcephaly (13q33.3-q34), cortical development malformations (13q33.1-qter), Dandy-Walker malformation (DWM) (13q32.2-q33.1), corpus callosum agenesis (CCA) (13q32.3-q33.1), meningocele/encephalocele (13q31.3-qter), DWM, CCA, and neural tube defects (NTDs) taken together (13q32.3-q33.1), ano-/microphthalmia (13q31.3-13qter), cleft lip/palate (13q31.3-13q33.1), lung hypoplasia (13q31.3-13q33.1), and thumb a-/hypoplasia (13q31.3-q33.1 and 13q33.3-q34). Based on observations of this study and previous reports we suggest a new entity, "distal limb anomalies association," linked to 13q31.3q33.1 segment. Most of the individuals with deletion of any part of 13q21qter showed surprisingly similar facial dysmorphic features, and thus, a "13q deletion facial appearance" was suggested. Prominent nasal columella was mapped between 13q31.3 and 13q33.3, and micrognathia between 13q21.33 and 13q31.1. The degree of mental delay did not display a particular phenotype-genotype correlation on chromosome 13. In contrast to previous reports of carriers of 13q32 band deletions as the most seriously affected patients, we present two such individuals with long-term survival, 28 and 2.5 years.

Genotype–phenotype correlations in patients with retinoblastoma and interstitial 13q deletions

“…A good candidate gene is PCDH9 that encodes for a cadherin-related neuronal receptor that localizes to synaptic junctions and has a putative role in specific neuronal connections and signal transduction. 31 Of note, all deletions found in our cohort are centromeric to 13q33.3q34, a region that was reported to be critical for microcephaly by Kirchhoff et al 30 Interestingly, a few patients in this cohort and in previous reports showed macrocephaly. 8,9 However, the pattern of deleted regions was the same as that in patients with normocephaly.…”

“…[27][28][29] Micrognathia was reported as a common dysmorphic feature in patients with 13q deletions and was associated with loss of the region 13q21.33q31.1. 30 Additional mild anomalies of the feet were found in 17 patients. Caselli et al 2007 also reported on toe crowding and a short V toe in 2/3 patients with an interstitial 13q deletion.…”

“…4,13,30,[38][39][40][41][42][43][44] Thus, analysis of the precise location and size of the deletion is needed to better inform families and physicians about the clinical expectations and survival in patients with a 13q deletion.…”

13q Deletion in a Girl Contributing to Antenatal Stroke, Insulin Resistance and Lymphedema Praecox: Expanding the Clinical Spectrum

“…Partial deletions in chromosome 13q lead to variable phenotypes based on the size and position of the deleted region [5]. While distal deletions are closely associated with severe phenotypes, proximal deletions tend to cause fewer major anomalies, with the exception of retinoblastoma [6].…”

Postnatal diagnosis of constitutive ring chromosome 13 using both conventional and molecular cytogenetic approaches

“…Lele et al (1963) first described a partial deletion of 13q in retinoblastoma patients who also displayed intellectual disabilities and global developmental delays . The 13q deletion syndrome leads to phenotypes that include short stature, microcephaly, cerebral cortical malformations, Dandy-Walker malformation (DWM), corpus callosum agenesis, meningocele/encephalocele, neural tube defects, micro-/anophthalmia, cleft lip/palate, lung hypoplasia, heart defects, genital anomalies, and hand abnormalities (Kirchhoff et al, 2009;Chen et al, 2013;Valdes-Miranda et al, 2014). In this study, we used 3 laboratory methodologies to report the first postnatal diagnosis in Central Brazil of a child with cytogenetic abnormalities involving chromosome 13.…”