Evaluation of Prevalence of PCOS and Associated Depression, Nutrition, and Family History: A Questionnaire-based Assessment.

Context: Polycystic ovarian syndrome (PCOS) is a common condition affecting women in the prime of reproductive age. The symptoms include infertility, amenorrhea, hirsutism, obesity, and androgenic alopecia. It is a socially stigmatizing condition and is often associated with depression, poor mental health, and quality of life. Settings and Design: We carried out a questionnaire based cross sectional study that assessed the prevalence of PCOS, collected information on the nutritional and life style related factors. A questionnaire was used to collect information with an intention to assess the prevalence of PCOS and to understand the contribution of life style/nutrition to the risk of PCOS. Student's t test and Z proportion test were used to assess significance and a 'p' value of ≤ 0.05 was considered significant. Results: A total of 972 females completed the questionnaire (mean age:24.37±8.37 years). Majority were from Telangana (n=823;84.67%) and students (690;70.98%). The mean weight was 60.58±13.03 kg and height was 1.78±2.56 m. Sizeable proportion reported irregular menstrual cycle (n=289;29.73%), that they get easily depressed: 283/972 (29.11%), low self-esteem:242/972 (24.90%), insomnia:223/972 (22.94%). A higher proportion of females were diabetic (8/243;3.29%Vs.10/706;1.42%;p=0.02) and non-vegetarian (69/243;28.40%Vs.119/706;16.86%;p=0.0002). No difference in the consumption of processed/fast food, carbonated drinks and lifestyle were noted. A significantly (p=0.0001) higher proportion of females had a positive family history (32/243;13.17%Vs.26/706;3.68%). Conclusion: Higher prevalence of PCOS was noted in young female population. Identifying at-risk individuals and imparting life style, nutrition-based modifications would be beneficial. Furthermore, regular counseling sessions might help tackle depression leading to a better overall physical and mental health.

Pooled genetic analysis identifies variants that confer enhanced susceptibility to PCOS in Indian ethnicity.

BACKGROUND: PCOS is a common endocrine disorder that is characterized by hyperandrogenism and chronic anovulation and is the leading cause of female infertility. It is a heterogeneous disorder with the involvement of multiple gene and environmental interactions. This study identified variants that are known to confer susceptibility identified by Genome wide association studies (GWAS) in other ethnicities and replicated the same in individuals with PCOS of Indian ethnicity. METHODS: Study subjects (n = 600) were recruited. Blood samples, demographic and clinical details were collected after obtaining informed consent. Fifteen variants were selected from GWA studies from other ethnicities and genotyped in half of the recruited samples (n = 300) using MassARRAYiPLEX™. Replication of significant variants generated from preliminary data was carried out by PCR and direct sequencing in remainder of the samples (n = 300). Insilco analysis for significant variants was performed using software namely CADD, GWAVA, FATHMM-MKL. Relevant statistics were used to ascertain significance. RESULTS: The mean age of patients and controls was 24.26 ± 3.22 and 30.19 ± 11.21 years respectively. Of the 15 variants, 3 variants (rs13405728 in LHCGR; rs13429458 in THADA and rs2209972 IDE genes) were found to be associated with PCOS. The association was successfully replicated in an independent cohort. Insilico analysis categorized two variants (rs13429458-THADA and rs2209972-IDE genes) as deleterious. CONCLUSION: We demonstrate the association of variants in genes namely LHCGR, THADA and IDE with an increased risk of PCOS. Genotyping for these variants aids in identifying at-risk individuals which is crucial as appropriate early interventions may benefit the patient.

Spectrum of mutations in the ATP binding domain of ATP7B gene of Wilson Disease in a regional Indian cohort.

Wilson disease is an autosomal recessive disorder of abnormal copper accumulation in the liver, brain, kidney and cornea, resulting in hepatic and neurological abnormalities, which results from impaired ATP7B protein function due to mutations in candidate ATP7B gene, till date more than 500 disease causing mutations were found. In India most disease causing mutations were identified in ATP-BD. DNA samples of the 101 WD cases and 100 control population were analyzed for mutations. 11 mutations were identified in 57 chromosomes. Three novel mutations, c.3310T>A (p.Cys1104Ser), c.3337C>A (p.Leu1113Met) on exon 15 and c.3877G>A (p.Glu1293Lys) on exon 18 were identified for the first time in the ATP7B gene. Two mutations, c.3121C>T (p.Arg1041Trp) and c.3128T>C (p.Leu1043Pro) on exon 14 were discovered for the first time in Indian Wilson disease patients. Four previously reported mutations c.3008C>T, c.3029A>G on exon 13, c.3182G>A on exon 14 and c.3809A>G on exon 18 from South India were also found in this study. Our research has enriched the spectrum of mutations of the ATP7B gene in the south Indian population. The detection of new mutations in the ATP7B gene can aid in genetic counseling and clinical or/prenatal diagnosis.

A dysmorphic child with a pericentric inversion of chromosome 8.

An 8-year-old boy was referred to our institute with dysmorphic features such as mild lupus, micrognathia, low hair line, hypoplasia, hemi atrophy of left side of the face, abnormal size of ears, hypothenar, hypoplasia of chin, and tongue tie. MRI scan was found to be normal and EEG suggestive of generalized seizure disorder. Cytogenetic evaluation of the proband revealed a pericentric inversion of chromosome 8 with 46, XY, and inv 8 (p11.2; q21.2) karyotype.

Distribution of CGG/GCC repeats at the FMR1 and FMR2 genes in an Indian population with mental retardation of unknown etiology.

AIMS: Fragile X syndrome is one of the X-linked disorders associated with moderate to severe mental retardation. Fragile X A syndrome (FRAXA) and fragile X E syndrome (FRAXE) are caused by trinucleotide repeat expansion of CGG and GCC repeats at the 5' untranslated region of the FMR1 and FMR2 genes, respectively. The present study was undertaken to identify the repeat polymorphism and to estimate the risk of transmission in Andhra Pradesh and surrounding states of South India. RESULTS: The FRAXA and FRAXE allelic polymorphisms were studied by radioactive polymerase chain reaction that revealed 25 FRAXA among 344 X-chromosomes and 20 FRAXE allelic variants among 212 X-chromosomes in our population. The most frequent FRAXA allele size was of 29 CGG repeats (27.5%) followed by allele sizes of 28 (20.8%) and 31 (7.2%), and that of FRAXE was 15 GCC repeats (24.0%) followed by allele containing 18 repeats (18.4%) and 16 repeats (11.3%). CONCLUSIONS: CGG/GCC repeat polymorphism at the FMR1 and FMR2 loci observed in this study demonstrated a racial and ethnic variation among the populations.