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Unmasking Genetic Mechanisms for Homocystinuria due to Methylenetetrahydrofolate Reductase Deficiency

Year: 2025

Type: article

Abstract: We report a female infant presenting with neonatal encephalopathy, seizures, and hyperhomocysteinemia. Genetic investigations revealed a homozygous variant, NM_005957.4 (methylenetetrahydrofolate reductase [MTHFR]): c.1031G>T; p. (Arg344Met). Unexpectedly, parental genetic testing showed maternal carrier status for MTHFR with paternal absence of the variant. Further genomic analysis, including autozygosity mapping confirmed maternal uniparental disomy (UPD) of chromosome 1 as the underlying genetic mechanism. The case underscores the importance of considering UPD in the diagnostic evaluation of autosomal recessive disorders, especially when parental carrier status does not align with expected inheritance patterns. Comprehensive genetic analysis, including segregation studies and advanced mapping tools, is crucial for accurate diagnosis, enabling targeted treatment and informed genetic counseling.

Source: Genetic Clinics

DOI: 10.4103/genc.genc_6_25

Authors: P. Muhammed Shabeer, Aakanksha Gahlot, Eshan Dabhade, Swasti Pal, Ratna D. Puri

Institution: Sir Ganga Ram Hospital

Language: English

Topic: Metabolism and Genetic Disorders

Subfield: Clinical Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

OpenAlex ID: W4408621439

FWCI:

Cites: 9

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Related to: 10