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A Novel Pathogenic TUBA1A Variant in a Croatian Infant Is Linked to a Severe Tubulinopathy with Walker–Warburg-like Features

Authors :
Akzam Saidin
Anet Papazovska Cherepnalkovski
Zeeshan Shaukat
Todor Arsov
Rashid Hussain
Ben J. Roberts
Marija Bucat
Klara Cogelja
Michael G. Ricos
Leanne M. Dibbens
Source :
Genes, Vol 15, Iss 8, p 1031 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Tubulinopathies are associated with malformations of cortical development but not Walker–Warburg Syndrome. Intensive monitoring of a Croatian infant presenting as Walker–Warburg Syndrome in utero began at 21 weeks due to increased growth of cerebral ventricles and foetal biparietal diameter. Monitoring continued until Caesarean delivery at 34 weeks where the infant was eutrophic. Clinical assessment of a progressive neurological disorder of unknown aetiology found a macrocephalic head and markedly hypoplastic genitalia with a micropenis. Neurological examination showed generalized hypotonia with very rare spontaneous movements, hypotonia-induced respiratory insufficiency and ventilator dependence, and generalized myoclonus intensifying during manipulation. With clinical features of hypotonia, lissencephaly, and brain malformations, Walker–Warburg Syndrome was suspected; however, eye anomalies were absent. Genetic trio analysis via whole-exome sequencing only identified a novel de novo mutation in the TUBA1A gene (NM_006009.4:c.848A>G; NP_006000.2:p.His283Arg) in the infant, who died at 2 months of age, as the likely cause. We report a previously unpublished, very rare heterozygous TUBA1A mutation with clinical features of macrocephaly and hypoplastic genitalia which have not previously been associated with the gene. The absence of eye phenotypes or mutations in Walker–Warburg-associated genes confirm this as not a new presentation of Walker–Warburg Syndrome but a novel TUBA1A tubulinopathy for neonatologists to be aware of.

Details

Language :
English
ISSN :
20734425
Volume :
15
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Genes
Publication Type :
Academic Journal
Accession number :
edsdoj.75e81de1fa4c4cffa40fd20a45a507f7
Document Type :
article
Full Text :
https://doi.org/10.3390/genes15081031