Molecular characterization of a cryptic 2q37 deletion in a patient with Albright hereditary osteodystrophy‐like phenotype

Abstract

The Albright hereditary osteodystrophy-like (AHO-like) syndrome was recently defined as a rare dysmorphic syndrome including brachymetaphalangism and mental retardation. This phenotype occurs in Albright hereditary osteodystrophy (AHO) but unlike it, the level of the Gs alpha protein activity is not reduced. To date 59 patients with these clinical and biochemical features have been reported, and for the majority of them (57/59) a cytogenetically visible 2q37 deletion has been observed. We report a new case of typical AHO-like syndrome with normal karyotype. Using the polymorphic marker D2S125 we found a loss of heterozygosity suggestive of a de novo 2q37 deletion of maternal origin. This hypothesis was confirmed by FISH analysis with a subtelomeric 2q probe containing the D2S90 marker. Genotypic analysis allowed us to map the proximal breakpoint of the subtelomeric deletion within an interval delimited by D2S2338 (present) and D2S2253 (deleted). This 2q subtelomeric deletion as small as 4 Mb is to date the smallest one observed in association with a typical AHO-like phenotype, and allows us to move the centromeric boundary of the AHO-like critical region by 750 kb towards the 2q telomere.

Loss of Heterozygosity at 2q37 in Sporadic Wilms' Tumor: Putative Role for miR-562

“…Thus, although this is one of the three germ-line rearrangements that inspired the study, the partial trisomy 15q likely also contributed to the pathogenesis of Wilms' tumor in this patient and the 2q37 deletion alone may not have been causal. In support of this, among the constitutional 2q37 deletions that have been well characterized at the DNA level, almost all harbor terminal deletions that extend proximally to HDAC4/ TWIST2 and are therefore deleted for both regions B and C, yet these patients do not have Wilms' tumor (19,(39)(40)(41)(42). In contrast, most of the proximal breakpoints localize distal of region A; in our panel of 30 deletion patients without malignancy, only one has a deletion of region A, with a breakpoint between NPPC and DIS3L2.…”

Class II Histone Deacetylases: from Sequence to Function, Regulation, and Clinical Implication

“…Consistent with this, Runx2 plays an essential role in bone development (36). More interestingly, the human HDAC4 gene is located at chromosome 2q37 (Table 2), a region whose abnormalities have been linked to Albright's hereditary osteodystrophy-like syndrome (20). The other two Runx proteins, Runx1 and Runx3, are important players in development and tumorigenesis (70).…”

The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients

“…A precise mapping of the deletions, however, was carried out in only a few studies (27/115 patients). [1][2][3][4][5][6][7][8][9][10]13,14,24,25,30,32 The patients with purely distal deletions (seven females, three males) included in the DECIPHER database (http://decipher.sanger.ac.uk/) had various deletion sizes ranging from 3 to 9.9 Mb. Unfortunately, clinical features were only mentioned for 2 of the 10 patients.…”