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We report a case of an X;1 translocation in a 9-month-old female infant with mild dysmorphic features and developmental delay. High-resolution chromosome analysis revealed a de novo, unbalanced translocation between chromosomes X and 1 [46,X,der(X),t(X;1)(q28;q32.1)]. Breakpoints on the derivative X and the size of the translocated segment have been defined by fluorescence in situ hybridization (FISH) with Xq and 1q specific probes. The rearrangement in this patient results in monosomy for Xq28-qter and trisomy for 1q32.1-qter. Replication studies demonstrated late replication of the derivative X in 80% of the observed cells, with the exception of 20% of the cells where X inactivation failed to spread into the translocated 1q segment. Patients with pure trisomy for the distal segment of 1q present a considerably more severe phenotype compared to that seen in our patient, including facial dysmorphisms, urogenital and cardiac anomalies. We suggest that the absence of many of the characteristic features for trisomy 1q in our patient, may reflect a mosaic pattern of inactivation of the translocated autosomal segment on the derivative X chromosome. © 2004 Wiley-Liss, Inc.

We report a 9-year-old girl with a mitochondrial cytopathy preceded by steroid-resistant focal segmental glomerulosclerosis (FSGS). The proband presented at the age of 2 years with steroid-resistant nephrotic syndrome caused by FSGS. Her renal function progressively deteriorated and a dilated cardiomyopathy developed at the age of 7 years. A skeletal muscle biopsy showed a combined respiratory chain (RC) defect and a partial deficiency of coenzyme Q10. A novel mutation in the evolutionary highly conserved region of the mitochondrial tRNATyr gene was found in homoplasmic state in skeletal muscle, blood, and renal tissue. The mutation was also found in homoplasmic state in her mildly symptomatic mother. No other maternal family members were available for testing. The present case of mitochondrial cytopathy initially presenting with steroid-resistant nephrotic syndrome, unusual biochemical and renal findings associated with a novel tRNA point mutation suggests that steroid-resistant FSGS can predate other features of mitochondrial disease for a prolonged period of time and that the progressive glomerulopathy associated with combined mitochondrial RC defects is genetically heterogeneous. © 2003 Wiley-Liss, Inc.

A 20-month-old girl with developmental delay, dysmorphic features, horizontal supranuclear gaze palsy, retrocollis, and episodes of laryngospasm was diagnosed with variant neuronopathic Gaucher disease. The diagnosis was made enzymatically. Mutation analysis showed compound heterozygosity for D409H and a previously unreported mutation C16S. The presence of dysmorphic features, laryngospasm, absent cardiac findings, and the severe clinical phenotype distinguishes our case from other cases of variant neuronopathic Gaucher disease. We therefore propose to extend the spectrum of variant Gaucher disease.

We report on a 22-month-old girl with minor facial anomalies, global developmental delay, growth retardation, seizures, and leukoencephalopathy. Initial clinical assessment suggested the diagnosis of Williams syndrome. Results of fluorescence in situ hybridization testing for elastin were normal. However, chromosome analysis showed a 46,XX,del(9)(p13.1p21.1) karyotype in peripheral lymphocytes. Parental chromosomes were normal, indicating a de novo deletion. This patient's manifestations are compared with those of two other cases with overlapping deletions of the proximal short arm of chromosome 9.