The TXNL4A gene is located on chromosome 18 at 18p23 and encodes a highly conserved component of the U5 spliceosomal complex that is essential for U4/U6·U5 tri-snRNP assembly, cell cycle progression and pre-mRNA splicing. TXNL4A was first reported in relation to autosomal recessive Burn-McKeown syndrome (BMKS) in 2014 (Wieczorek et al., PMID: 25434003). BMKS is a rare multiple congenital anomaly syndrome characterized by bilateral choanal atresia associated with characteristic cranio-facial dysmorphisms and generally normal intelligence. Other phenotypes may include hearing loss, cleft lip/palate, and cardiac defects. At least 10 unique variants (promoter, missense, nonsense, frameshift) that have been reported in 14 probands in four publications (PMIDs: 25434003, 28905882, 32187816, 34713892) are included in this curation. Twelve out of the 14 probands were compound heterozygotes with a 34 bp promoter type 1 deletion (NM_006701.5:c.-222_-189del34) identified on one allele and a loss-of-function variant on the other. This gene-disease relationship is also supported by evidence of functional alteration, and an animal model in Xenopus (PMIDs: 25434003, 32735620, 35893124). In summary, there is definitive evidence to support the relationship between TXNL4A and autosomal recessive Burn-McKeown syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Syndromic GCEP on the meeting date 2/16/2024 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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