NM_014362.3(HIBCH):c.220-9T>G AND Beta-hydroxyisobutyryl-CoA deacylase deficiency

Significance: Pathogenic
ClinVar: RCV000001203

Variant: NM_014362.3(HIBCH):c.220-9T>G

Type: Variant
Allele: NM_014362.3(HIBCH):c.220-9T>G 16183
Type: single nucleotide variant
Location: Chr2: 191159365 - assembly GRCh37
Chr2: 190294639 - assembly GRCh38
References: dbSNP: 786200864
OMIM: 610690.0001


Disease: Beta-hydroxyisobutyryl-CoA deacylase deficiency


    In the patient with 3-hydroxyisobutyryl-CoA hydrolase deficiency (HIBCHD; 250620) with progressive infantile neurodegeneration and structural abnormalities of the brain and heart reported by Brown et al. (1982), Loupatty et al. (2007) identified a homozygous IVS3-9T-G mutation in the HIBCH gene. This T-to-G transversion only slightly weakens the consensus sequence for a splice acceptor site, since a pyrimidine is preferred over a purine at this position in the consensus sequence. Hence, Loupatty et al. (2007) investigated by analysis of HIBCH cDNA obtained by RT-PCR from skin fibroblast RNA the consequence of the mutation on splicing efficiency. Sequence analysis of the amplicon revealed a homozygous 8-bp insertion after the last base of exon 3, causing a frameshift (Lys73fsTer86). The 8-bp insertion resulted from retention of the 3-prime end of intron 3. Missplicing was evident; only the aberrant spliced transcript could be detected.
PMID:17160907, PMID:7122152