title: A novel gross indel in the growth hormone releasing hormone receptor gene of Indian IGHD patients.
abstract: BACKGROUND
  Cohort specific mutations in the growth hormone (GH1) and growth hormone-releasing hormone receptor (GHRHR) genes have been reported worldwide in isolated growth hormone deficiency (IGHD) patients. However, limited data is available on ethnically diverse Indian IGHD patients.
  
  
  OBJECTIVE
  The aim of the study was to find GH1 and GHRHR gene mutations in Indian IGHD patients from two unrelated non-consanguineous families.
  
  
  METHODS
  The 5' and 3' untranslated regions (UTRs) and coding regions with splice sites of the GH1 and GHRHR genes were sequenced for all patients (n=6). Family members and 20 controls were evaluated for the sequence variants identified in the index patients. Online bioinformatics tools were used to confirm mutations and their pathogenicity.
  
  
  RESULTS
  GHRHR gene mutations were observed in all patients. Interestingly, a novel indel g.30999250_31006943delinsAGAGATCCA was observed in both the unrelated families. Three patients were homozygous for the novel indel, two were homozygous for the previously reported p.E72X mutation and one was compound heterozygous with both the mutations (indel and p.E72X) in the GHRHR gene. The novel indel has resulted in the loss of 5' regulatory region and exon 1 of the GHRHR gene impairing the GHRHR expression. All the normal family members were heterozygous either for the indel or p.E72X mutation. None of the patients had GH1 gene mutations.
  
  
  CONCLUSIONS
  We describe a novel gross indel in the GHRHR gene resulting in the loss of 5' regulatory region and GHRHR exon 1 in four IGHD IB patients from two unrelated non-consanguineous Indian families.
authors.affiliation: Department of Endocrinology, Seth G.S. Medical College, K.E.M. Hospital, Parel, Mumbai 400012, India. Electronic address: svk82004@gmail.com.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Kale
authors.affiliation: Department of Endocrinology, Seth G.S. Medical College, K.E.M. Hospital, Parel, Mumbai 400012, India.
authors.forename: Sweta
authors.initials: S
authors.lastname: Budyal
authors.affiliation: Department of Endocrinology, Seth G.S. Medical College, K.E.M. Hospital, Parel, Mumbai 400012, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Kasaliwal
authors.affiliation: Department of Endocrinology, Seth G.S. Medical College, K.E.M. Hospital, Parel, Mumbai 400012, India.
authors.forename: Vyankatesh
authors.initials: V
authors.lastname: Shivane
authors.affiliation: Department of Endocrinology, Seth G.S. Medical College, K.E.M. Hospital, Parel, Mumbai 400012, India.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Raghavan
authors.affiliation: Department of Endocrinology, Seth G.S. Medical College, K.E.M. Hospital, Parel, Mumbai 400012, India.
authors.forename: Anurag
authors.initials: A
authors.lastname: Lila
authors.affiliation: Department of Endocrinology, Seth G.S. Medical College, K.E.M. Hospital, Parel, Mumbai 400012, India.
authors.forename: Tushar
authors.initials: T
authors.lastname: Bandgar
authors.affiliation: Department of Endocrinology, Seth G.S. Medical College, K.E.M. Hospital, Parel, Mumbai 400012, India.
authors.forename: Nalini
authors.initials: N
authors.lastname: Shah
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004393:Dwarfism, Pituitary / Q000453:epidemiology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006579:Heterozygote; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D007194:India / Q000453:epidemiology; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*
chemical_list: D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D019382:Human Growth Hormone; C048250:somatotropin releasing hormone receptor
keywords: GHRHR; IGHD; Indian; Novel gross indel