Simmi K Ratan1, Anju Sharma2, Seema Kapoor3, Sunil K Polipalli2, Divya Dubey4, Tarun K Mishra2, Shandip K Sinha5, Satish K Agarwal5. 1. Department of Pediatric Surgery, Maulana Azad Medical College and Associated LokNayak Hospital, G-8/6, Second Floor, Malviya Nagar, New Delhi, 110017, India. drjohnsimmi@yahoo.com. 2. Department of Biochemistry, Maulana Azad Medical College and Associated LokNayak Hospital, New Delhi, India. 3. Department of Pediatrics, Maulana Azad Medical College and Associated LokNayak Hospital, New Delhi, India. 4. Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India. 5. Department of Pediatric Surgery, Maulana Azad Medical College and Associated LokNayak Hospital, G-8/6, Second Floor, Malviya Nagar, New Delhi, 110017, India.
Abstract
OBJECTIVE: To study MAMLD1 gene polymorphisms, serum LH and testosterone levels amongst Indian children with isolated hypospadias (IH) and controls. MATERIALS AND METHODS: Screening of the MAMLD1 gene was performed by PCR sequencing method in 100 Indian children aged 0-12 years presenting with IH and 100 controls. LH and testosterone hormone levels were also assessed (categorized in four age-wise groups). RESULTS: IH subjects had significantly higher incidence of MAMLD1 polymorphism as compared to controls (33 vs 15 %, p = 0.01). Of various genomic variants identified in this study, the noteworthy novel ones were missense mutation P299A and single nucleotide polymorphism c.2960C>T in 3' UTR of Exon 7. While p 299A was found to cause protein structural instability consequent to amino acid change, eighty percent subjects with c.2960C>T in 3' UTR of Exon 7 (corresponding to newly discovered currently non-validated exon 11) were found to have lower testosterone levels when compared with their age group mean. IH showed statistically higher incidence of c.2960C>T in comparison to controls (22 vs 10 %, p value 0.046) and about 2.5-folds higher risk of this anomaly. CONCLUSION: Occurrence of MAMDL1 gene polymorphisms, specially of c.2960C>T in 3' UTR of its exon 7 is associated with a higher risk of IH in Indian children, probably by lowering androgenic levels.
OBJECTIVE: To study MAMLD1 gene polymorphisms, serum LH and testosterone levels amongst Indian children with isolated hypospadias (IH) and controls. MATERIALS AND METHODS: Screening of the MAMLD1 gene was performed by PCR sequencing method in 100 Indian children aged 0-12 years presenting with IH and 100 controls. LH and testosterone hormone levels were also assessed (categorized in four age-wise groups). RESULTS: IH subjects had significantly higher incidence of MAMLD1 polymorphism as compared to controls (33 vs 15 %, p = 0.01). Of various genomic variants identified in this study, the noteworthy novel ones were missense mutation P299A and single nucleotide polymorphism c.2960C>T in 3' UTR of Exon 7. While p 299A was found to cause protein structural instability consequent to amino acid change, eighty percent subjects with c.2960C>T in 3' UTR of Exon 7 (corresponding to newly discovered currently non-validated exon 11) were found to have lower testosterone levels when compared with their age group mean. IH showed statistically higher incidence of c.2960C>T in comparison to controls (22 vs 10 %, p value 0.046) and about 2.5-folds higher risk of this anomaly. CONCLUSION: Occurrence of MAMDL1 gene polymorphisms, specially of c.2960C>T in 3' UTR of its exon 7 is associated with a higher risk of IH in Indian children, probably by lowering androgenic levels.
Authors: J Laporte; L J Hu; C Kretz; J L Mandel; P Kioschis; J F Coy; S M Klauck; A Poustka; N Dahl Journal: Nat Genet Date: 1996-06 Impact factor: 38.330