A unique patient with an Ullrich–Turner syndrome variant and mosaicism for a tiny r(X) and a partial proximal duplication 1q

Abstract

A 7-year old female with global cognitive impairment, short attention span, hyperactivity, impulsivity, and many compulsive behaviors was referred to the Genetics Clinic. Height was below the 5th centile and weight was at the 5th centile while head circumference was at the 50th centile. Minor anomalies included bluish sclera, low set and slightly posteriorly rotated auricles and a narrow palate with marked overbite. There was no significant family history. Chromosome analysis showed an unbalanced, mosaic female karyotype consisting of three cell lines: 46,X,+r[46]/45,X[37]/45,X,dup(1)(q11q21.3) [17] de novo.ish r(X)(DXZ1+,XIST+). Expression of XIST was observed in cDNA from the patient, suggesting the presence of an inactive X chromosome. Inactivation was confirmed by detection of a methylated allele of androgen receptor. This methylated allele was under-represented in undigested DNA, consistent with it arising from the r(X) which was present in only a minority of the patient's cells. The clinical phenotype of the tiny r(X) syndrome in our patient is obviously further influenced by mosaicism for the dup(1). Few cases of duplication of the proximal portion of chromosome 1 have been reported. Of these, the duplication either was present in all cells or involved different band regions so that a direct comparison would be difficult. However, the lower percentage of mosaicism for the dup(1) in our patient would suggest a milder influence on the clinical phenotype.