Novel mutation in HPRT1 causing a splicing error with multiple variations.

Area of Science:

• Genetics
• Biochemistry
• Neurology

Background:

• Lesch-Nyhan disease (LND) is a rare X-linked recessive disorder.
• It results from deficiency of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme, encoded by the HPRT1 gene.
• While various HPRT1 mutations are known, duplication mutations are exceptionally rare.

Observation:

• A 9-month-old boy presented with LND symptoms including developmental delay, athetosis, and dystonic posture.
• The patient exhibited hyperuricemia and complete deficiency of HPRT enzyme activity in erythrocytes.
• Notably, the patient did not display self-injurious behaviors, a common LND manifestation.

Findings:

• A novel duplication mutation (c.372dupT, c.372_374 TTT > c.372_375 TTTT) was identified in exon 4 of the HPRT1 gene.
• This mutation was found to cause aberrant splicing of the HPRT1 gene.
• This represents the third reported case of a duplication mutation in HPRT1 leading to splicing errors.

Implications:

• This case expands the known spectrum of HPRT1 mutations causing LND.
• Understanding novel mutations like this duplication is crucial for accurate genetic diagnosis and counseling.
• Further research into HPRT1 splicing defects may reveal new therapeutic targets for LND.