• PMID: 20506135
• Gene Name: SOHLH1
• Condition: Nonobstructive azoospermia
• Association: This deletion results in SOHLH1 with a truncated bHLH domain. Transient transfection assay showed that the SOHLH1 mutant with the truncated domain disrupted the transcriptional activity of KIT promoter, whereas two missense mutations harboring either p.Ar
• Mutation: one intronic variant (c.346-1G>A), and two nonsynonymous exonic variants (c.91T>C and c.529C>A) with known single nucleotide polymorphisms (SNPs)
• Population size: 96
• Population details: 96 Korean patients with NOA
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Nonobstructive azoospermia

Mutations in SOHLH1 gene associate with nonobstructive azoospermia

Choi Y, Jeon S, Choi M, Lee MH, Park M, Lee DR, Jun KY, Kwon Y, Lee OH, Song SH, Kim JY, Lee KA, Yoon TK, Rajkovic A, Shim SH.

In a previous study, we found SOHLH1 (spermatogenesis and oogenesis-specific basic helix-loop-helix 1) as the first testis-specific basic helix-loop-helix transcription factor essential for spermatogonial differentiation. SOHLH1 therefore represents an excellent candidate gene for testicular failure such as nonobstructive azoospermia (NOA). We analyzed whether there were mutations in the SOHLH1 gene in 96 Korean patients with NOA. The sequence analysis discovered three novel variations: one intronic variant (c.346-1G>A), and two nonsynonymous exonic variants (c.91T>C and c.529C>A) with known single nucleotide polymorphisms (SNPs), which included six intronic variants, two synonymous, and two nonsynonymous variants. We examined the consequences of mutations in SOHLH1 using in vivo and in vitro assays. Analysis of transcripts from minigenes carrying the c.346-1G>A revealed that splicing site variation leads to the partial deletion at a cryptic splicing site within exon 4. This deletion results in SOHLH1 with a truncated bHLH domain. Transient transfection assay showed that the SOHLH1 mutant with the truncated domain disrupted the transcriptional activity of KIT promoter, whereas two missense mutations harboring either p.Arg37Gln or p.Pro269Ser did not have a significant effect on its transactivation. Our findings indicate that a splice-acceptor site mutation that probably causes a nonfunctional SOHLH1 protein results in nonobstructive azoospermia by the lack of normal spermatogenesis. CI - (c) 2010 Wiley-Liss, Inc. FAU - Choi, Youngsok AU - Choi Y AD - Department of Biomedical Science, CHA University, Seoul, Republic of Korea. shshim@cha.ac.kr FAU - Jeon, Sanghyun AU - Jeon S FAU - Choi, Mikyung AU - Choi M FAU - Lee, Min-ho AU - Lee MH FAU - Park, Miseon AU - Park M FAU - Lee, Dong Ryul AU - Lee DR FAU - Jun, Kyu-Yeon AU - Jun KY FAU - Kwon, Youngjoo AU - Kwon Y FAU - Lee, Ok-Hee AU - Lee OH FAU - Song, Seung-Hun AU - Song SH FAU - Kim, Ji-Young AU - Kim JY FAU - Lee, Kyung-Ah AU - Lee KA FAU - Yoon, Tae Ki AU - Yoon TK FAU - Rajkovic, Aleksandar AU - Rajkovic A