Aquarius^® Microdeletion Syndrome probes

Kallmann (KAL1) and Steroid Sulphatase Deficiency (STS) Combination Probe LPU016 - Detail

Kallmann syndrome (KS) is a developmental disease characterised by olfactory deficiency and hypogonadotrophic hypogandism (HH), which is responsible for the absence of spontaneous puberty¹. It is a heterogeneous developmental genetic disorder affecting about 1 in 8,000 males and 1 in 40,000 females². Reports indicate three modes of inheritance: X-linked, autosomal dominant and autosomal recessive ^1,3,4. It has been shown that mutations in KAL1 on Xp22.3 result in the X-linked form⁵. KAL1 consists of 14 exons and extends over 210 kb⁶. KAL1 gene abnormalities reported in patients with KS include missense and nonsense mutations, splice site mutations, intragenic deletions and submicroscopic chromosomal deletions involving the entire KAL1 gene⁷.

Steroid Sulphatase Deficiency (STS) (also known as X-linked Ichthyosis) ⁸ is the second most common type of ichthyosis and one of the most frequent human enzyme deficiency disorders. Deficiency of the STS enzyme⁹ is known to be responsible for dark, adhesive and regular scaling of the skin. The STS gene is mapped at the distal part of the short arm of the X chromosome, region which escapes X-chromosome inactivation and has the highest ratio of chromosomal deletions among all genetic disorders¹⁰. Complete deletions have been found in more than 90% of patients¹¹. The deletions can extend to involve neighbouring genes causing contiguous gene defect. Therefore, STS may be associated with KS¹².

The KAL1 Region probe labelled in red, is approximately 336 kb, contain markers DXS278, DXS7470, DXS7714, DXS7053 and covers the entire KAL1 gene and flanking DNA. The accompanying STS Region probe, labelled in green, consists of two clones: a 173 kb clone containing marker DXS7731 and a 149 kb clone containing markers DXS6767, DXS7965, DXS7500. They cover the entire STS gene and flanking DNA. The X centromere probe: DXZ1 (Xp11.1-q11.1) probe, labelled in green, acts as a control. In the normal XY cell, there should be one red and two green signals (1R, 2G) or fusion of the red and green signals (yellow) and one green control signal (1Y, 1G), whilst a deletion of a probe target results in no red/yellow signal and one green control signal (0R, 1G) (KAL1/STS deletion) or (1R, 1G)(STS deletion) or (0R, 2G) (KAL1 deletion). In the normal XX cell, there should be two red and four green (2R, 4G) or two yellow and two green (2Y, 2G) signals, whilst a deletion of a probe target results in 1Y, 2G (KAL1/STS deletion) or 1Y,1R,2G (STS deletion) or 1Y,3G (KAL1 deletion).