MRPL44 and Hypertrophic Cardiomyopathy

MRPL44 mutations have been implicated in a multisystem disorder primarily characterized by childhood‑onset hypertrophic cardiomyopathy, with additional features such as renal insufficiency, liver abnormalities, and pigmentary retinopathy. These findings underscore the importance of MRPL44 in mitochondrial translation and energy metabolism (PMID:25797485).

The disorder follows an autosomal recessive inheritance pattern. In the reported studies, two siblings from one family were found to be homozygous for the missense mutation, while two additional unrelated patients carried either a homozygous or compound heterozygous mutation. In total, four probands have been reported (PMID:25797485), with segregation evident in familial clusters.

Genetic evidence is robust with multiple variant classes identified. A recurrent variant, selected here as the representative finding, is c.467T>G (p.Leu156Arg). Other observed variants include c.467T>C (p.Leu156Pro) and c.233G>A (p.Arg78Gln). This spectrum of missense mutations supports pathogenicity through disruption of protein function within the mitochondrial ribosome (PMID:25797485).

Segregation analysis across the families indicates that at least two additional affected relatives exhibit the disease phenotype consistent with the presence of pathogenic MRPL44 variants. Such familial evidence further bolsters the gene‐disease assertion by demonstrating co‐segregation of the mutation with the clinical phenotype (PMID:25797485).

Functional assessments have demonstrated that defects in mitochondrial translation due to MRPL44 mutations lead to combined respiratory chain deficiency. Experimental studies, including in vitro assays, recapitulate key aspects of the clinical phenotype, thereby establishing that the pathogenic mechanism likely involves loss of function leading to mitochondrial dysfunction (PMID:25797485).

In summary, the convergence of genetic data from four probands with clear familial segregation and functional studies that corroborate the mitochondrial defect provide strong evidence for the role of MRPL44 mutations in hypertrophic cardiomyopathy. Key take‑home: Recognizing MRPL44 deficiency as the underlying cause supports precise diagnostic decision‑making and informs both patient management and future therapeutic development.

References

• Neurogenetics | 2015 | MRPL44 mutations cause a slowly progressive multisystem disease with childhood‑onset hypertrophic cardiomyopathy PMID:25797485

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