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DNAH14 (HGNC:2945) is implicated in autosomal recessive neurodevelopmental disorders through identification of compound heterozygous variants in three unrelated probands (PMID:35438214). Trio whole‐exome sequencing revealed one nonsense, one frameshift and four missense variants, including c.6100C>T (p.Arg2034Ter), absent or at low frequency in gnomAD and predicted damaging by multiple bioinformatics tools, with four changes in the AAA+ ATPase domain and two in the C‐terminal domain.
Affected individuals presented with global developmental delay, hypotonia, seizures and microcephaly, consistent with disrupted dynein motor function. No extended familial segregation or in vivo/in vitro functional models have been reported; pathogenicity is currently supported by conservation and in silico data. Further genetic and functional studies are required to establish causality and guide diagnostics. Key take-home: DNAH14 compound heterozygous variants represent a potential autosomal recessive cause of neurodevelopmental disorder.
Gene–Disease AssociationLimited3 unrelated probands with compound heterozygous variants in DNAH14 (PMID:35438214), without extended segregation or experimental modeling Genetic EvidenceLimitedCompound heterozygous nonsense, frameshift and missense variants in 3 probands (PMID:35438214) Functional EvidenceLimitedPathogenicity supported primarily by in silico predictions and conservation |