Lenz-Majewski syndrome: Report of a case with novel mutation in PTDSS1 gene.

Lenz-Majewski syndrome (LMS) is an extremely rare syndrome characterized by osteosclerosis, intellectual disability, characteristic facies and distinct craniofacial, dental, cutaneous and distal - limb anomalies. Recently, mutations in PTDSS1 gene have been identified as causative in six unrelated individuals. We report the seventh mutation proven case of LMS and provide a concise review of all known patients till date.

Mutational analysis of methyl-CpG binding protein 2 (MECP2) gene in Indian cases of Rett syndrome.

Rett syndrome (RTT) is an X-linked postnatal neurological disorder, primarily affecting females and characterized by regression, epilepsy, stereotypical hand movements, and motor abnormalities. Its prevalence is about 1 in 10,000 female births. RTT is caused by mutations within methyl CpG-binding protein 2 (MECP2) gene. Over 200 individual nucleotide changes in the gene, which cause pathogenic mutations, have been reported; however, eight most commonly occurring missense and nonsense mutations account for almost 70% of all mutations. RTT cases have also been reported from India. The phenotype (classical and atypical inclusive) has many differentials. However, a genetically based confirmed diagnosis would help in management and counseling. In this pilot study we have analyzed MECP2 mutations in ten Indian sporadic patients diagnosed clinically as having RTT. Two mutations and one novel variant in MECP2 have been detected. Missense mutations p.R133C and c.806delG have been detected. The missence mutation p.R133C was the part of eight hotspots reported in Rett patients. This patient met all the essential criteria except delayed onset of regression. The other c.806delG mutation positive patient also fulfilled all the obligatory criteria of classical RTT. Another clinically atypical Rett patient showed a novel mutation p.C339S in MECP2 gene. The preliminary result necessitates a large-scale study of RTT patients to determine more precisely the influence of MECP2 mutations in Indian patients and their correlation with clinical phenotypes.

Validity of analysis of FMRP expression in blood smears as a screening test for Fragile X Syndrome in the Indian population.

Molecular diagnosis of Fragile X Syndrome (FXS) is carried out by PCR or Southern blot analysis on DNA isolated from leukocytes. These DNA analyses are time consuming and expensive, making it impractical for mass screening programs. We have recently standardized and tested the diagnostic potential of a rapid antibody test on blood smears, based on the presence of FMRP, the protein product of the FMR1 gene, in lymphocytes from normal individuals and the absence of FMRP in lymphocytes in patients with FXS. This test is essentially similar to the one developed at Erasmus University in the Netherlands, with suitable modifications. The diagnostic power of the antibody test is perfect for males, whereas the results are less specific for females. The cutoff value for affected male individuals, expressed as the percentage of FMRP-positive cells, was 20%. In normal individuals, the cutoff value was 85%. The results of the antibody test correlated well with that of Southern blots. Sensitivity of the test was 100% and specificity was 97.5%. This noninvasive test requires one or two drops of blood and is rapid, simple, and cheap, making it an ideal choice for large screening large groups of male mental retardates and neonates for FXS in developing countries such as India.

Tel-Hashomer camptodactyly syndrome with hirsuitism in an Indian family.

Two new cases with the Tel-Hashomer camptodactyly syndrome have been ascertained in an Indian family. This report emphasizes the autosomal recessive nature of disease and documents an additional feature of hirsuitism not previously described. The gene for Tel-Hashomer camptodactyly syndrome is present in all populations around the world.