No abstract

Two isozymes of steroid 5a-reductase encoded by separate loci catalyze the conversion of testosterone to dihydrotestosterone. Inherited defects in the type 2 isozyme lead to male pseudohermaphroditism in which affected males have a normal internal urogenital tract but external genitalia resembling those of a female. The 5a-reductase type 2 gene (gene symbol SRD5A2) was cloned and shown to contain five exons and four introns. The gene was localized to chromosome 2 band p23 by somatic cell hybrid mapping and chromosomal in situ hybridization. Molecular analysis of the SRD5A2 gene resulted in the identification of 18 mutations in 11 homozygotes, 6 compound heterozygotes, and 4 inferred compound heterozygotes from 23 families with 5a-reductase deficiency. 6 apparent recurrent mutations were detected in 19 different ethnic backgrounds. In two patients, the catalytic efficiency of the mutant enzymes correlated with the severity of the disease. The high proportion of compound heterozygotes suggests that the carrier frequency of mutations in the 5a-reductase type 2 gene may be higher than previously thought. (J. Clin. Invest. 1992. 799-809.)

Dystroglycan is a novel laminin binding component of the dystrophin-glycoprotein complex which provides a linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. Here we report the cDNA and genomic structure of human dystroglycan. The human dystroglycan is encoded by a single gene (DAG1) mapped to chromosome 3 band p21. The coding sequence is organized into two exons, separated by a large intron. The predicted amino acid sequence of human and rabbit dystroglycan are 93% identical with predicted glycosylation sites being conserved. Human dystroglycan is expressed in a variety of fetal and adult tissues. Our data suggest that muscle and non-muscle isoforms of dystroglycan differ by carbohydrate moieties but not protein sequence. Therefore, we hypothesize that variable glycosylation of the conserved protein core might modulate laminin binding. The relationship of dystroglycan to human diseases is discussed.

Deletions of chromosome 6q are rare. We report 3 new patients with 6q deletions. Case 1 is a male with an interstitial deletion [del(6)(q13q14.2)], hypotonia, speech delays, and minor anomalies. Case 2 is a male with an interstitial deletion [del(6)(q16.2q22.32)] and malformations, including truncus arteriosus and bilateral oligodactyly. Case 3 is a male with a terminal deletion [del(6)(q25.2)] with retinal pits, hydrocephalus, atrioventricular canal, and hydronephrosis. The findings in our patients and those from 57 previously reported cases demonstrated 3 phenotypic groups associated with 6q deletions. Group A [del(6)(q11-q16)] had a high incidence of hernias, upslanting palpebral fissures, and thin lips with lower frequency of microcephaly, micrognathia, and heart malformations. Group B [del(6)(q15-q25)] was associated with increased intrauterine growth retardation, abnormal respiration, hypertelorism, and upper limb malformations. Group C [del(6)(q25-qter)] was associated with retinal abnormalities, cleft palate, and genital hypoplasia. The only universal finding among all patients with 6q deletions was mental retardation. Other findings common to all 3 groups included ear anomalies (90%), hypotonia (82%), and postnatal growth retardation (68%).