Clinical and experimental reproductive medicine · 2026
A novel loss-of-function variant in DNHD1 linked to human asthenozoospermia.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Nawaz Shoaib, Shaheen Sidrah, Nasir Abdul, Khan Hammal, Nayab Anam, Khan Ranjha, Umair Muhammad
Аннотация
OBJECTIVE: Asthenozoospermia, characterized by diminished sperm motility, shows substantial genetic heterogeneity. Although many familial cases of asthenozoospermia have been documented, the genetic etiology for most affected males remains unknown.
METHODS: This study used clinical and molecular approaches to characterize a hereditary form of asthenozoospermia. Two patients born to consanguineous parents exhibited impaired sperm motility. Whole-genome sequencing (WGS), followed by Sanger sequencing, was performed for molecular diagnosis and was coupled with three-dimensional protein modeling to characterize the identified variant.
RESULTS: WGS revealed that both affected brothers carried a pathogenic variant (c.580C>T; p.Gln194*) in dynein heavy chain domain 1 (DNHD1). Homozygous variants in DNHD1 have previously been linked to spermatogenic failure 65 (Online Mendelian Inheritance in Man [OMIM] 619712). Three-dimensional protein modeling demonstrated significant alterations in DNHD1 secondary structure that could contribute to loss-of-function.
CONCLUSION: These findings support a role for DNHD1 in maintaining the structural and functional integrity of sperm. Accurate molecular diagnosis may facilitate genetic counseling and inform clinical management.
METHODS: This study used clinical and molecular approaches to characterize a hereditary form of asthenozoospermia. Two patients born to consanguineous parents exhibited impaired sperm motility. Whole-genome sequencing (WGS), followed by Sanger sequencing, was performed for molecular diagnosis and was coupled with three-dimensional protein modeling to characterize the identified variant.
RESULTS: WGS revealed that both affected brothers carried a pathogenic variant (c.580C>T; p.Gln194*) in dynein heavy chain domain 1 (DNHD1). Homozygous variants in DNHD1 have previously been linked to spermatogenic failure 65 (Online Mendelian Inheritance in Man [OMIM] 619712). Three-dimensional protein modeling demonstrated significant alterations in DNHD1 secondary structure that could contribute to loss-of-function.
CONCLUSION: These findings support a role for DNHD1 in maintaining the structural and functional integrity of sperm. Accurate molecular diagnosis may facilitate genetic counseling and inform clinical management.