Reciprocal translocation between the proximal regions of the long arms of chromosomes 13 and 15 resulting in unbalanced offspring: characterization by fluorescence in situ hybridization and DNA analysis

Abstract

We describe two female siblings with similar clinical features consisting of hydrocephalus, scaphocephaly, hypotonia, mongoloid eye slant, blepharophimosis, micrognathia, supernumerary mouth frenula and mental retardation. Routine cytogenetic studies in the elder patient did not reveal any abnormality, and initially it was assumed that the syndrome had an autosomal recessive inheritance. However, a slightly larger chromosome 13 was seen in routine G-banded metaphases of the mother and the youngest of the two siblings. A shorter chromosome 15 was detected in the mother only. High resolution banding showed that the abnormal chromosome 13 contained an extra G-positive band at 13q12. The short chromosome 15 in the mother appeared to have a deletion of band q12. Fluorescence in situ hybridization using DNA markers specific to chromosomes 13 and 15 unequivocally showed that the mother was a carrier of a balanced reciprocal translocation t(13;15)(q12;q13), whereas the youngest sibling's karyotype was 46,XX,-13,+der(15)t(13;15)(q12;q13)mat, resulting in partial monosomy 13pter----q12 and partial trisomy 15pter----q13. The proband is thus trisomic for the critical region responsible for Prader-Willi syndrome and Angelman syndrome; this was confirmed by DNA analysis demonstrating one paternal and two maternal alleles from multiallelic marker loci mapping to 15q11-q13. This report illustrates the sensitivity and specificity offered by fluorescence in situ hybridization and its usefulness in the diagnosis and delineation of subtle chromosomal rearrangements.

Prenatal diagnosis of a new case: De novo balanced non-Robertsonian translocation involving t(15;22)(p11.2;q11.2)

“…Mangelschots et al . [3] reported a case with 46,XX,t(13;15)(q12;q13) where she gave birth to a child with karyotype 46,XX,+13,+der(15)t(13;15)(q12;q13)mat. Most of the ROBs are balanced in relation to acrocentric chromosomes with the breakpoints (q10; q10).…”

A rare balanced nonrobertsonian translocation involving acrocentric chromosomes: Chromosome abnormality of t(13;15)(p11.2;q22.1)

“…Mangelschots et al . [ 9 ] reported a case with 46, XX, t(13;15)(q12;q13) where she gave birth to a child with karyotype 46, XX,-13, +der (15) t(13;15)(q12;q13) mat. Most of the RTs are balanced involving acrocentric chromosomes with the breakpoints (q10;q10).…”

Molecular cytogenetic characterization of an interstitial de novo 13q deletion in a 3‐month‐old with severe pediatric gastroesophageal reflux

“…Interstitial deletions of proximal long arm of chromosome 13, not including the Retinoblastoma locus, are extremely rare with only 10 cases reported [Suzuki et al, 1977; Cohen et al, 1978; Otto et al, 1978; Prieto et al, 1979; Palmer et al, 1987; Geormaneanue and Geormaneanu, 1990; Slee et al, 1991; Colley et al, 1992; Mangelschots et al, 1992; Drummond‐Borg et al, 2002]. Of these, only the patient reported by Drummond‐Borg et al 2002 appears to be similar to our case.…”

“…Of these, only the patient reported by Drummond‐Borg et al 2002 appears to be similar to our case. Also, 4 of the 10 cases have additional chromosome imbalance due to unbalanced segregation of a balanced rearrangement in one of the parent [Suzuki et al, 1977; Otto et al, 1978; Prieto et al, 1979; Mangelschots et al, 1992]. One of the consistent features seen with these proximal 13q deletions is microcephaly, which is seen in 4 of the 10 patients.…”