• ring (22)
• deletion 22q13
• parental origin
• phenotype-genotype correlations
• telomere

The terminal regions of human chromosomes are known to contain specialised DNA sequences and may be vulnerable to rearrangements causing human genetic diseases and particularly idiopathic mental impairment.^1,2 During the last decade, there have been several reports of patients who are described as having a 22q13 monosomy resulting from simple terminal deletions.^1,3–11 A common phenotype emerged from these reports, including variable learning difficulties with disproportionate verbal delay, generalised hypotonia, normal to accelerated growth, and minor facial dysmorphy.¹⁰ Monosomies for 22q13 have also been reported that result from unbalanced translocation with an acrocentric short arm.^10,12 The acrocentric short arms only bear ribosomal genes, and their duplication or deletion is not generally thought to be phenotypically significant. Therefore such translocations can be considered as “pure” terminal 22q13 deletions.

A distinct group of 22q13 monosomies has been reported that result from the formation of a ring chromosome which combines loss of some long arm material with loss of part of the short arm, with no clinical consequences. Nevertheless, although ring chromosome 22 has been described in over 50 cases,¹³ it remains uncertain whether the variable phenotype is caused by the loss of a variable amount of chromosomal material or by a cellular mosaicism arising from instability of the ring.

Regardless of the causative rearrangement, very few cases of “pure” 22q13 monosomy have been investigated up to now by detailed molecular studies. In order to characterise this syndrome better, facilitate the diagnosis, and provide targeted health care for affected individuals, we have studied 33 patients (32 new observations) with a pure 22q13 partial monosomy, using molecular and cytogenetic methods.