Recessive loss of DIAPH1 function causes a progressive neurodevelopmental syndrome with variable immunological involvement.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Galassi Deforie Valentina, Maroofian Reza, Karagoz Irem, Godwin Annie, Al Sheikh Ebtehal, Gestri Gaia, Zaki Maha S, Woodward Beth L, Ghorab Raghda M, Alvi Javeria Raza, Alabdi Lama, Damseh Nadirah, Elshafie Reem M, Scardamaglia Annarita, Alves Cesar, Shaikh Mahum, Özcan Güliz Gürel, Sadek Abdelrahim A, Issa Mahmoud Y, Striano Pasquale, Suri Mohnish, Murphy David, Ashhab Motee, de la Fuente Rubén Pérez, Arteche-López Ana, Hashem Mais O, Abdulwahab Firdous, Aboelanine Ashraf H, Alkhawaja Issam Azmi, Ibrahim Shahnaz, van der Burg Mirjam, Berghuis Dagmar, Santen Gijs We, Toosi Mehran Beiraghi, Alerasool Masoome, Eslahi Atieh, Srinivasan Varunvenkat M, Gowda Vykuntaraju K, Trollmann Regina, Vasileiou Georgia, Pauly Melissa, Hashemi-Gorji Farzad, Miryounesi Mohammad, Salpietro Vincenzo, Al-Herz Waleed, Carter Stephen P, Briggs Tracy A, Hussell Tracy, Ruuska-Loewald Terhi, Komulainen-Ebrahim Jonna, Uusimaa Johanna, Hautala Timo, Potluri Sandeep, Shackley Fiona, Mojarrad Majid, Chung Wendy K, Wilson Stephen W, Sultan Tipu, Gleeson Joseph G, Marafi Dana, Alkuraya Fowzan S, Stewart Grant S, Efthymiou Stephanie, Guille Matthew, Arkwright Peter D, Houlden Henry
Аннотация
METHODS: A total of 53 individuals with biallelic DIAPH1 variants, including 33 previously unreported patients, were studied. Clinical features were analyzed, and functional studies were conducted using knockout models in Danio rerio and Xenopus tropicalis.
RESULTS: Clinical features included developmental delay, intellectual disability, progressive microcephaly, cortical visual impairment or blindness, epilepsy, and frequent occipital-predominant brain abnormalities. Almost half suffered from infections, mainly affecting their respiratory tract related to epilepsy and aspiration. Although the majority had normal lymphocyte subsets and serum immunoglobulins, T cell receptor excision circles and naïve T-lymphocyte counts were consistently low. The Xenopus model mirrored growth and eye defects seen in humans, whereas zebrafish exhibited no overt malformations but showed seizure-like behavior in Phenothiazine assays.
CONCLUSION: DIAPH1 is critical for neurodevelopment, immune regulation, and DNA repair. The DNA repair defect may influence susceptibility to infection, lymphoma, or treatment-related toxicity. Although absolute T cell numbers are not consistent with SCID, impaired T cell maturation suggests that these patients could be identified by T cell excision circles newborn screening before neurological symptoms develop.