Novel Compound Heterozygous Variants in the LHCGR Gene in a Genetically Male Patient with Female External Genitalia
| Autor: | Yiping Shen, Julaiti Dilihuma, Maimaiti Mireguli, Baoerhan Reyilanmu, Mei Yan, Yanfei Luo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Sanger sequencing Genetics endocrine system Mutation Sexual differentiation business.industry Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism medicine.disease medicine.disease_cause Compound heterozygosity 03 medical and health sciences symbols.namesake Exon 030104 developmental biology 0302 clinical medicine Endocrinology Pediatrics Perinatology and Child Health Leydig cell hypoplasia medicine symbols Missense mutation business Exome sequencing |
| Zdroj: | Journal of Clinical Research in Pediatric Endocrinology. 11:211-217 |
| ISSN: | 1308-5735 1308-5727 |
| DOI: | 10.4274/jcrpe.galenos.2018.2018.0197 |
| Popis: | The LHCGR gene encodes a G-protein coupled receptor that plays a pivotal role in sexual differentiation in males, ovarian development in females and in fertility via its interaction with luteinizing hormone and chorionic gonadotropin. Inactive variants of the LHCGR gene cause Leydig cell hypoplasia (LCH), which is a rare disease and one of the causes of disorder of sexual differentiation (DSD) in males. The aim of this work was to clarify the clinical and molecular characteristics of a 2.75 year old patient with type 1 LCH. Whole exome sequencing was performed for the patient family and variants in the LHCGR gene were validated by Sanger sequencing. Pathogenicity of the missense variant was evaluated by multiple in silico tools. Our Chinese patient, who exhibited DSD, had female external genitalia (normal labia majora and minora, external opening of urethra under the clitoris and blind-ended vagina) and bilateral testis tissues in the inguinal region. Genetic sequencing revealed compound heterozygous variants in the LHCGR gene in the patient, including a novel missense variant in exon 4 (c.349G>A, p.Gly117Arg) and a novel nonsense variant in exon 10 (c.878C>A, p.Ser293*). The missense variant is in the first leucine-rich repeat domain of the LHCGR protein, which is predicted to affect ligand recognition and binding affinity and thus protein function. The patient is molecularly and clinically diagnosed with type 1 LCH, which is caused by novel, compound heterozygous variants of the LHCGR gene. We believe this report will serve to expand the genotypic spectrum of LHCGR variants. |
| Databáze: | OpenAIRE |
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