X-linked recessive chondrodysplasia punctata: spectrum of arylsulfatase E gene mutations and expanded clinical variability.

X-linked chondrodysplasia punctata (CDPX1), due to mutations of the arylsulfatase E (ARSE) gene, is a congenital disorder characterized by abnormalities in cartilage and bone development. We performed mutational analysis of the ARSE gene in a series of 16 male patients, and we found mutations in 12 subjects. Clinical variability was observed among the patients, including severe presentations with early lethality in one of them, and symptoms such as cataract and respiratory distress. This indicates that the clinical spectrum of CDPX1, commonly considered a relatively mild form of chondrodysplasia punctata, is wider than previously reported. Different types of mutations were found among the patients examined. Three missense mutations (I80N, T481M, P578S) were expressed in Cos7 cells to study the effects on arylsulfatase E catalytic activity. These mutations caused impaired enzymatic activity suggesting that they are responsible for the disease. Two nonsense mutations, W581X in four patients and R540X in one, were found. One patient showed an insertion (T616ins). In three patients we found deletions of the ARSE gene: in one the deletion involved only the 3' end of the gene, while in two the ARSE gene was completely deleted.

Unbalanced translocation (3;5)(q26.1;p14): a clinical report.

A patient with a multiple congenital anomalies/mental retardation (MCA/MR) syndrome had an unbalanced translocation (3;5)(q26.1;p14), causing partial 5p monosomy and partial 3q trisomy. The phenotype observed in this patient results from the combination of those described in the isolated dup(3q) and del(5p) syndromes. Some clinical features of this patient are shared by the Smith-Lemli-Opitz syndrome (SLOS), a well-known MCA/MR syndrome due to the deficiency of 7-dehydrocholesterol reductase (DHCR7). We review the previously reported cases of chromosomal anomalies with clinical features suggesting SLOS.