Paracentric inversion involving the long arm of chromosome 9 resulting in deletion of abl gene

Abstract

We report on a new chromosomal finding in a newborn male with hypertelorism, apparently low-set malformed ears with patent canal, micrognathia with narrow high-arched palate, bilateral webbing of neck with low posterior hairline, widely spaced nipples, and complex heart anomalies. Initially, what appeared to be a simple paracentric inversion of the long arm of chromosome 9, that is, 46,XY, inv(9)(q31q34) by routine GTG-banding technique was later determined to be a paracentric inversion with deletion of the band 9q34.1 by FISH technique using an abl unique sequence DNA probe. Thus the cytogenetic diagnosis was modified to 46,XY,der(9) inv(9)(q31q34.1)del(q34.1). Nevertheless, the presence of telomeric repeat sequences in the inverted chromosome 9 suggests that either healing has occurred by adding [TTAGGG]n sequences to the non-telomeric end (q31) by the enzyme telomerase or telomeric sequences were not affected during this inversion process. This abnormality is a rare occurrence and has never been reported before either because of a high rate of lethality or it has been undetected by routine cytogenetic techniques. The other abnormal cases with apparent paracentric inversions could also have a complex nature with congenital anomalies associated with loss of "few" DNA sequences as exemplified here.

Interstitial 9q34.11–q34.13 deletion in a patient with severe intellectual disability, hydrocephalus, and cleft lip/palate

“…ABL1 is a protooncogene that encodes for a tyrosine kinase known best for its fusion product of the t(9;22) translocation (Philadelphia chromosome) involved in chronic myelogenous leukemia (CML). Deletions of ABL1 were detected by FISH analysis in two patients with chromosome rearrangements: In a patient with cardiac defect and a paracentric inversion inv(9)(q31q34.1) [Kleyman et al, 1997] and in a patient with a maternally inherited translocation t(3;22;9)(q22;q12;q34.1) [Aboura et al, 2003]. The sizes of these deletions were not determined, and those patients bore no clinical resemblance to the patient reported here.…”

Cloacal exstrophy in an infant with 9q34.1‐qter deletion resulting from a de novo unbalanced translocation between chromosome 9q and Yq

“…A review of the literature revealed 14 observations of pure partial 9q deletion with variable breakpoints [Newton et al, 1972; Smith et al, 1973; Jenkins et al, 1976; Wisniewski et al, 1977; Turleau et al, 1978; Ying et al, 1982; Schinzel, 1988; Farrell et al, 1991; Park et al, 1991; Pfeiffer et al, 1991; Schimmenti et al, 1994; Shimkets et al, 1996; Ayyash et al, 1997; Kleyman et al, 1997]. Only three of them included 9q34.1‐qter region [Schimmenti et al, 1994; Ayyash et al, 1997; Kleyman et al, 1997] and no characteristic phenotype emerged (Table I). Only facial anomalies and hypotonia were consistently found.…”

Deletion in the ABL gene resulting from a meiotic recombination of a maternal (3;22;9)(q22;q12;q34.1) translocation

“…The first case described was a newborn with dysmorphism and a complex cardiac anomaly. 19 The main phenotypic anomaly observed in the child was axial hypotonia. As emphasised by Kleyman et al, 19 comparison of this cryptic deletion 9q34.1 with previous reports involving large deletions may be irrelevant.…”

“…19 The main phenotypic anomaly observed in the child was axial hypotonia. As emphasised by Kleyman et al, 19 comparison of this cryptic deletion 9q34.1 with previous reports involving large deletions may be irrelevant. Hypotonia was also observed in a case of deletion 9q32q34 described by Turleau et al 20 Recently, mutations in the gene encoding c-Abl-binding protein SH3BP2 were reported to cause cherubism.…”