Characterization of a 5.8-Mb Interstitial Deletion of Chromosome 3p in a Girl with 46,XX,inv(7)dn Karyotype and Phenotypic Abnormalities

Abstract

Interstitial deletions of the short arm of chromosome 3 are rare, and a specific clinical phenotype has not been defined. We report the first isolated cryptic proximal interstitial 3p deletion, del(3)(p12.3p13), assessed by array-based comparative genomic hybridization in a girl with an inversion of chromosome 7, whose phenotype includes neurodevelopmental delay, growth retardation, dysmorphic facial features, hypophysis hypoplasia, gastroesophageal reflux, clinodactyly, preauricular appendix, and myopia. Her features are similar to those observed in the previously reported cases of proximal 3p deletions overlapping with our imbalance, indicating that her clinical manifestations are likely to be due to the deletion. As our patient’s imbalance is the first non-cytogenetically visible proximal interstitial 3p deletion uncomplicated by other imbalances, its characterization has allowed us to narrow the minimal deletion interval associated with growth retardation and neurodevelopmental delay to the 3p12.3–p13 region. Among the genes found in this region, ROBO1, ROBO2, PDZRN3 and CNTN3 might play a role in the neurodevelopmental delay of the patient. This study provides additional evidence that cryptic imbalances anywhere along the genome can be found in patients with phenotypic abnormalities and a balanced chromosome rearrangement.

3p14 deletion is a rare contiguous gene syndrome: Report of 2 new patients and an overview of 14 patients

“…Our three patients shared at least some of their clinical features with the other 11 reported individuals with proximal interstitial chromosome 3p deletion (Table and Fig. ) [Petek et al, ; Lalli et al, ; Schwarzbraun et al, ; Morales et al, ; Pariani et al, ; Carr et al, ; Horn et al, ; Tao et al, ; Ţuţulan‐Cunită et al, ].…”

“…We selected 11 out of 26 published cases with overlapping deletions for comparison because of their detailed phenotypic description and molecular characterization (Fig. ) [Petek et al, ; Lalli et al, ; Schwarzbraun et al, ; Morales et al, ; Pariani et al, ; Carr et al, ; Horn et al, ; Tao et al, ; Ţuţulan‐Cunită et al, ]. The results are summarized in Table and the critical regions for some of the phenotypic features are indicated in Figure .…”

“…Twenty‐six patients with a proximal interstitial chromosome 3p deletion encompassing the 3p14 band have been reported in the literature [Kogame and Kudo, ; Wyandt et al, ; Sichong et al, ; Mitter et al, ; Neri et al, ; Short et al, ; Hertz et al, ; Naritomi et al, ; Karimi‐Nejad et al, ; Crispino et al, ; Wieczorek et al, ; Pfeiffer et al, ; Schinzel et al, ; Petek et al, ; Lalli et al, ; Schwarzbraun et al, ; Morales et al, ; Pariani et al, ; Carr et al, ; Horn et al, ; Tao et al, ; Ţuţulan‐Cunită et al, ]. Their clinical features have been reviewed in the past but no consensus has been reached regarding a specific, recognizable phenotype.…”

“…Their clinical features have been reviewed in the past but no consensus has been reached regarding a specific, recognizable phenotype. This may be, at least partly, due to the small cohort size of reported cases, different age at presentation, and limited molecular data regarding the exact deletion size and break point coordinates [Neri et al, ; Schinzel et al, ; Lalli et al, ; Morales et al, ; Pariani et al, ].…”

“…Here we describe the detailed phenotyping of three patients with 3p14p12 deletions characterized by aCGH. Their phenotypes and molecular karyotypes have been aligned against 11 published cases with clinically and molecularly well‐characterized chromosome 3p rearrangements [Petek et al, ; Lalli et al, ; Schwarzbraun et al, ; Morales et al, ; Pariani et al, ; Carr et al, ; Horn et al, ; Tao et al, ; Ţuţulan‐Cunită et al, ]. Common features suggest that chromosome 3p14 deletion is a distinct multiple congenital anomalies contiguous gene syndrome.…”