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Autosomal recessive mandibuloacral dysplasia (MAD) due to biallelic MTX2 variants is a recently described skeletal dysplasia characterized by postnatal growth retardation (HP:0008897), hypotonia (HP:0001252) and generalized lipodystrophy (HP:0009064). A single unrelated 6-year-old patient presenting with these features underwent whole-exome sequencing, which identified a novel homozygous c.543+1G>T splice site variant in MTX2 ([PMID:36269149]). Patient RNA analysis by RT-PCR and Sanger sequencing confirmed exon 8 skipping, consistent with loss-of-function. No additional affected family members or segregation data are available. On the basis of one proband with molecular splicing confirmation and absence of replication, the gene–disease association is classified as Limited. Diagnostic MTX2 testing informs clinical surveillance and genetic counseling for affected families.
Gene–Disease AssociationLimitedOne unrelated proband with biallelic MTX2 splice variant and molecular splicing confirmation; no additional families or segregation data Genetic EvidenceLimitedBiallelic null MTX2 variant identified in a single case of MAD; no further segregation (PMID:36269149) Functional EvidenceModeratePatient RNA analysis confirmed exon 8 skipping for c.543+1G>T, consistent with loss-of-function (PMID:36269149) |