Novel Mutations Involving the INSL3 Gene Associated With Cryptorchidism

Brahim El Houate, Hassan Rouba, Hicham Sibai, Abdelhamid Barakat, Abdelaziz Chafik, El bekkay Chadli, Laila Imken, Natalia Bogatcheva, Shu Feng, Alexander I. Agoulnik, Ken McElreavey

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Purpose: Cryptorchidism affects 1% to 9% of full-term male neonates. Hypospadias is the second most frequent congenital anomaly seen in newborn males. These pathological conditions are part of the testicular dysgenesis syndrome. Insulin-like factor 3 and LGR8 (leucine-rich repeat-containing G protein-coupled receptor 8), acting as a hormone and a receptor, respectively, are involved in control of the first phase of testicular descent via gubernacular development. Materials and Methods: The study group consisted of 184 patients, of whom 52 presented with unilateral cryptorchidism, 37 presented with bilateral cryptorchidism, 19 presented with cryptorchidism and hypospadias, 1 presented with bilateral cryptorchidism and micropenis, and 75 presented with isolated hypospadias. A control panel consisted of 270 controls, including 127 fertile, and 143 fertile noncryptorchid males. Insulin-like factor 3 mutations were analyzed by direct sequencing and restriction enzyme digestion. We analyzed the ability of the mutant insulin-like factor 3 peptides identified in this study to activate LGR8 receptor in an ex vivo assays. Results: We identified 3 novel insulin-like factor 3 variants, including C-19G, V18M and R105H, in 3 of the 109 patients (2.75%) but in none of the 270 controls. The V18M mutation in the insulin-like factor 3 signal peptide had a significant deleterious effect in activating LGR8 receptor in ex vivo studies (p

Original languageEnglish (US)
Pages (from-to)1947-1951
Number of pages5
JournalJournal of Urology
Volume177
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

Fingerprint

Cryptorchidism
Hypospadias
Insulin
Mutation
Genes
Newborn Infant
Protein Sorting Signals
G-Protein-Coupled Receptors
Leucine
Digestion
Hormones
Peptides
Enzymes

Keywords

  • cryptorchidism
  • hypospadias
  • mutation
  • penis
  • urethra

ASJC Scopus subject areas

  • Urology

Cite this

El Houate, B., Rouba, H., Sibai, H., Barakat, A., Chafik, A., Chadli, E. B., ... McElreavey, K. (2007). Novel Mutations Involving the INSL3 Gene Associated With Cryptorchidism. Journal of Urology, 177(5), 1947-1951. https://doi.org/10.1016/j.juro.2007.01.002

Novel Mutations Involving the INSL3 Gene Associated With Cryptorchidism. / El Houate, Brahim; Rouba, Hassan; Sibai, Hicham; Barakat, Abdelhamid; Chafik, Abdelaziz; Chadli, El bekkay; Imken, Laila; Bogatcheva, Natalia; Feng, Shu; Agoulnik, Alexander I.; McElreavey, Ken.

In: Journal of Urology, Vol. 177, No. 5, 05.2007, p. 1947-1951.

Research output: Contribution to journalArticle

El Houate, B, Rouba, H, Sibai, H, Barakat, A, Chafik, A, Chadli, EB, Imken, L, Bogatcheva, N, Feng, S, Agoulnik, AI & McElreavey, K 2007, 'Novel Mutations Involving the INSL3 Gene Associated With Cryptorchidism', Journal of Urology, vol. 177, no. 5, pp. 1947-1951. https://doi.org/10.1016/j.juro.2007.01.002
El Houate B, Rouba H, Sibai H, Barakat A, Chafik A, Chadli EB et al. Novel Mutations Involving the INSL3 Gene Associated With Cryptorchidism. Journal of Urology. 2007 May;177(5):1947-1951. https://doi.org/10.1016/j.juro.2007.01.002
El Houate, Brahim ; Rouba, Hassan ; Sibai, Hicham ; Barakat, Abdelhamid ; Chafik, Abdelaziz ; Chadli, El bekkay ; Imken, Laila ; Bogatcheva, Natalia ; Feng, Shu ; Agoulnik, Alexander I. ; McElreavey, Ken. / Novel Mutations Involving the INSL3 Gene Associated With Cryptorchidism. In: Journal of Urology. 2007 ; Vol. 177, No. 5. pp. 1947-1951.
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abstract = "Purpose: Cryptorchidism affects 1{\%} to 9{\%} of full-term male neonates. Hypospadias is the second most frequent congenital anomaly seen in newborn males. These pathological conditions are part of the testicular dysgenesis syndrome. Insulin-like factor 3 and LGR8 (leucine-rich repeat-containing G protein-coupled receptor 8), acting as a hormone and a receptor, respectively, are involved in control of the first phase of testicular descent via gubernacular development. Materials and Methods: The study group consisted of 184 patients, of whom 52 presented with unilateral cryptorchidism, 37 presented with bilateral cryptorchidism, 19 presented with cryptorchidism and hypospadias, 1 presented with bilateral cryptorchidism and micropenis, and 75 presented with isolated hypospadias. A control panel consisted of 270 controls, including 127 fertile, and 143 fertile noncryptorchid males. Insulin-like factor 3 mutations were analyzed by direct sequencing and restriction enzyme digestion. We analyzed the ability of the mutant insulin-like factor 3 peptides identified in this study to activate LGR8 receptor in an ex vivo assays. Results: We identified 3 novel insulin-like factor 3 variants, including C-19G, V18M and R105H, in 3 of the 109 patients (2.75{\%}) but in none of the 270 controls. The V18M mutation in the insulin-like factor 3 signal peptide had a significant deleterious effect in activating LGR8 receptor in ex vivo studies (p",
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AU - Chadli, El bekkay

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