A novel deletion mutation in the DSG4 gene underlies autosomal recessive hypotrichosis with variable phenotype in two unrelated consanguineous families.

BACKGROUND: Autosomal recessive hypotrichosis is a rare human hereditary disorder presenting as sparse scalp hair or as woolly hair occurring on various parts of the body. Various forms of isolated hypotrichosis have been reported to date. Mutations in at least 11 genes have been reported to cause hypotrichosis. AIMS: To investigate the clinical and genetic basis of autosomal recessive hypotrichosis in two unrelated consanguineous families. METHODS: Genotyping by highly polymorphic microsatellite markers established linkage in both families to the DSG4 gene on chromosome 18q21. PCR amplification of exons and intron-exon borders of the DSG4 gene was performed, and the products sequenced to search for disease-causing sequence variants. RESULTS: Clinical investigation revealed typical hypotrichosis in the affected members of one family, while other affected members showed presence of monilethrix-like scalp hair. Sequence analysis of DSG4 revealed a novel deletion mutation (c.85-1_191del) in the affected subjects of both families. CONCLUSIONS: This study further extends the body of evidence that mutations in the DSG4 gene result in both hypotrichosis and monilethrix-like scalp hair.

Mutations in the P2RY5 gene underlie autosomal recessive hypotrichosis in 13 Pakistani families.

BACKGROUND: Autosomal recessive hypotrichosis is a rare genetic irreversible hair loss characterized by sparse scalp hair, sparse to absent eyebrows and eyelashes, and sparse axillary and body hair. Affected male individuals have normal beard hair. OBJECTIVES: To search for pathogenic mutations in the human P2RY5 gene in Pakistani families with autosomal recessive hereditary hypotrichosis. METHODS: In the present report, 16 unrelated consanguineous Pakistani families having multiple affected individuals with autosomal recessive hypotrichosis were investigated. Linkage in these families was searched by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci LAH1, LAH2 and LAH3. Thirteen of the families showed linkage to the LAH3 locus on chromosome 13q14.11-q21.32. These families were then subjected to direct sequencing of the P2RY5 gene, which encodes a G protein-coupled receptor. RESULTS: Sequence analysis of the P2RY5 gene revealed two novel missense mutations (c.742A>T; p.N248Y and c.830C>T; p.L277P) in three families. Five previously described mutations including three missense (c.188A>T; p.D63V, c.436G>A; p.G146R, c.562A>T; p.I188F), one insertion (c.69insCATG; p.24insHfsX52) and one complex deletion (c.172-175delAACT; 177delG; p.N58-L59delinsCfsX88) were detected in the other 10 families. CONCLUSIONS: Mutations revealed in the present study extend the body of evidence implicating the P2RY5 gene in the pathogenesis of human hereditary hair loss.

Lipoprotein (a) and glycaemic control in Pakistani subjects with diabetes mellitus.

AIMS: To measure lipoprotein (Lp)(a) levels in people with diabetes mellitus (DM) and to see if there is any difference in Lp(a) levels between diabetics with good glycaemic control and those with poor glycaemic control. METHODS: Sixty subjects with DM and thirty healthy individuals were studied. Fasting blood samples were analyzed for glucose, glycosylated hemoglobin, Serum total cholesterol, triglycerides, low density lipoproteins, high density lipoproteins and Lp(a). RESULTS: A non significant difference was found between the lipid profile of normal individuals and subjects with DM with a good glycemic control. Lp(a) levels were significantly raised in diabetics. The difference in Lp(a) levels between well controlled and poorly controlled diabetics was non significant. In the control group 23.4% of individuals had high risk levels of Lp(a) while it was 46.7 % for people with DM. CONCLUSION: Glycaemic control improves lipid profile positively in diabetics and may even lead to near normalization of lipoprotein concentrations. Diabetics have elevated levels of Lp(a) and the difference in Lp(a) levels between well controlled and poorly controlled diabeticsts is non-significant.

Demonstration of the site of obstruction in azoospermia by biochemical markers.

This study was carried out on 25 patients with azoospermia and normal serum FSH levels signifying obstruction as its cause. To determine the site of obstruction semen transferrin levels, carnitine and fructose were estimated. Patients with an obstruction at the testis-epididymal junction had low levels of transferrin but normal levels of carnitine and fructose. Patients who had lower levels of transferrin and carnitine, but normal levels of fructose had obstruction at the epididymal level, probably in the tail of the epididymis. Obstruction of the ejaculatory ducts was signified by lower levels of all parameters in the semen. Our study showed that levels of transferrin, carnitine and fructose when used in conjunction with each other could localize the site of obstruction in azoospermia.