Rare interstitial deletion (2)(p11.2p13) in a child with pericentric inversion (2)(p11.2q13) of paternal origin

Abstract

An unbalanced 46,XY,der(2)del(2)(p11.2p13) inv(2)(p11.2q13) karyotype was found in a phenotypically abnormal child with a de novo interstitial deletion of band 2p12 associated with an inv(2)(p11.2q13) inherited from the father. The inv(2) is generally considered a benign familial variant without significant reproductive consequences. However, our findings led us to consider a previously proposed mechanism of unequal meiotic crossing over at the base of a parental inversion loop, which could lead to either a deletion or duplication of a segment adjacent to the inverted region in the offspring. This phenomenon has been reported in other inversions of chromosomes 1, 7, 13, 15, and 17 and may explain the origin of the deletion in our patient. Although repetitive sequences might be present around such inversions, which could predispose to de novo deletions independently of the inversion, current evidence including this case favors a proposed causal relationship between the parental inversion and the deletion in the child. Our review and results suggest there could be a small risk for a related imbalance to couples with an inv(2)(p11.2q13). For del(2)(p11.2p13), which is rare, a more distinct phenotype has been proposed herein. Our patient shared several findings with the three previously published cases, namely the broad nasal bridge, abnormal ears, high-arched palate, psychomotor retardation, and micrognathia. However, our patient also had sensorineural hearing loss and significant hypotonia, which have not been previously reported, thereby expanding our understanding of this rare deletion. Am. J. Med. Genet. 87:139-142, 1999. Published 1999 Wiley-Liss, Inc.

Contribution of SNP arrays in diagnosis of deletion 2p11.2–p12

“…The majority of the reported deletions of chromosome 2 involved the bands 2pl1-2p15 (Duca et al, 1981;Lacbawan et al, 1999;Los et al, 1994;Prasher et al, 1993;Wenger and McPherson, 1997).…”

Unrelated patients with a rearrangement of chromosome 2 causing duplication of 2p23 and deletion of 2q37

“…Early publications described increased reproductive wastage, but no liveborns with an unbalanced recombination of a parental pericentric inversion 2 [Djalali et al, 1986]. Then Magee et al [1998] and Lacbawan et al [1999] described offspring with chromosome abnormalities possibly related to their fathers' inversions; and Richter et al [1989] and Angle et al [2000] documented liveborns with recombinant 2s with duplication of 2q material and deletion of 2p material (opposite to our patients).…”

Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2

“…Skull and vertebral bone abnormalities included slight asymmetry of the appearance of the orbits and delayed closure of the metopic suture in Subject 1 and congenital C1-C2 vertebral fusion, and accentuation of dorsal kyphosis in Subject 2. Previous cases with cytogenetic deletions/disruptions of this region all had developmental delay and the majority had head/facial anomalies, ear and skeletal abnormalities [1,2]. …”

“…Chromosomal abnormalities involving the 2p13 chromosomal region were detected previously in subjects with developmental delay using traditional chromosome testing [1,2]. Abnormal features present in at least 50% of cases included abnormal head size/shape, nose, ears, chest and vertebral, digital and genital anomalies.…”