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

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.

Identification of a dup(5)(p15.3) by multicolor banding.

A 7-year-old female was referred to the Genetics Clinic because of developmental delay and attentional difficulty. The patient was adopted and there was a nonspecific prenatal history of drug and alcohol abuse. The patient had clinical signs that were not compatible with typical fetal alcohol syndrome (FAS), although there was a history of alcohol exposure in utero, neurodevelopmental difficulties with learning and behavioral problems, and mild dysmorphisms. Cytogenetic analysis revealed an unbalanced female karyotype with a dup(5) containing additional chromosome 5 material at band 5p15.3. The dup(5) showed normal copy number of the cri-du-chat region on 5p15.2 using locus-specific probes D5S721 and D5S23. Multicolor banding of chromosome 5 (MetaSystems) using partial chromosome paint (pcp) probes showed a duplication of band 5p15.3. The karyotype of the patient was therefore interpreted as follows: 46,XX,add(5)mat.ish dup(5)(p15.3)(wcp5 +, D5S271 +, D5S23 +, C84C11/T3 + +, pcp5p15.3 + +). The patient's biological mother and maternal half-brother were found to carry the identical chromosome duplication. The clinical phenotype of the biological mother is complicated by a difficult lifestyle but there were apparent learning and behavioral difficulties at school. The half-brother is nondysmorphic and presents with learning problems and attention deficit disorder (ADD). His physical examination was normal. To the best of our knowledge, this is the first report of a limited duplication of 5p15.3. The clinical significance of the dup(5)(p15.3) is still uncertain but may be the basis for learning and attention difficulties.

Fragile 19p13 in a family with mental illness.

We describe a family where four brothers show the rare heritable folate sensitive autosomal fragile site (FSAFS) at 19p13 when cells were grown in TC199. Two of the brothers are schizophrenic while one brother is mentally retarded with autistic-like features. The clinical significance of this fragile site however is still unknown.