Genetic analysis of a Chinese pedigree with Lesch-Nyhan syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology for a Chinese pedigree affected with Lesch-Nyhan syndrome.@*METHODS@#Members of the pedigree who had visited the Genetic Counseling Clinic of Linyi People's Hospital on February 10, 2022 were selected as the study subjects. Clinical data and family history of the proband were collected, and trio-whole exome sequencing (trio-WES) was carried out for the proband and his parents. Candidate variants were verified by Sanger sequencing.@*RESULTS@#Trio-WES revealed that both the proband and his cousin brother had harbored a hemizygous c.385-1G>C variant in intron 4 of the HPRT1 gene, which was unreported previously. A heterozygous c.385-1G>C variant of the HPRT1 gene was also found in the proband's mother, grandmother, two aunts, and a female cousin, whilst all phenotypically normal males in his pedigree were found to have a wild type for the locus, which has conformed to an X-linked recessive inheritance.@*CONCLUSION@#The heterozygous c.385-1G>C variant of the HPRT1 gene probably underlay the Lesch-Nyhan syndrome in this pedigree.

Choreoathetosis and dystonia in a child with COVID­19 and multisystem inflammatory syndrome

Neurological complications of COVID-19 or multisystem inflammatory syndrome in children (MIS-C) are well described. We report an unusual presentation in a 9-year-old girl presenting with status epilepticus, who thereafter developed choreoathetosis and dystonia. She was initially managed with intravenous immunoglobulins and methylprednisolone for presumed autoimmune encephalitis. However, she tested positive for SARS-CoV-2 and met the clinical and laboratory criteria for MIS-C. She remained encephalopathic with abnormal movements and dystonia for 8 days from presentation but was discharged home with complete clinical recovery after 2 weeks.

Síndrome de Lesch-Nyhan y automutilación oral. Reporte de un caso / Oral self-mutilation in Lesch-Nyhan Syndrome. Case Report

Resumen: Introducción: El síndrome de Lesch-Nyhan (SLN) es un trastorno hereditario recesivo relacionado con el cromosoma X, causado por la deficiencia de la enzima hipoxantina-guanina fosforribosil transferasa (HPRT). La automutilación compulsiva y distonía ocurre antes del año de edad y se expresa con mordeduras persistentes en la mucosa oral, labios, lengua, dedos y hombros. La intervención odontológica realizada en la mayoría de estos pacientes es la extracción dental múltiple para prevenir lesiones graves secundarias. Objetivo: presentar un caso clínico de SLN y describir el manejo odonto-pediátrico en pacientes con conducta automutilatoria. Caso clínico: Paciente varón, 7 años de edad, portador de SLN. Fue referido a la Unidad de Odontología desde el Departamento de Neurología Pediátrica para la evaluación y manejo de heridas autoinfligidas en dedos, labios y mejillas asociadas a una pérdida de peso y disminución de la ingesta de alimentos. El procedimiento quirúrgico consistió en extracciones dentales múltiples, y remodelación quirúrgica de las crestas alveolares residuales, bajo anestesia general. Al segundo mes posquirúrgico el paciente fue dado de alta definitivamente, con un adecuado estado nutricional y sin signos de automutilación en manos ni en cavidad oral. Conclusio nes: A pesar, que el SLN es infrecuente, es esencial saber cómo proceder para dar la mejor calidad de vida a los pacientes y sus familias. Las extracciones tempranas del diente, como fase inicial en casos severos, parecen ser la alternativa más útil para minimizar el daño y el dolor por la automutilación.

Abstract: Introduction: Lesch-Nyhan syndrome (LNS) is an inherited recessive X-related disorder caused by the deficiency of the enzyme hypoxanthin-guanine phosphorribosyl transferase (HPRT). Compul sive self-mutilation and dystonia occurs before the first year of age and is expressed by persistent bites on the oral mucosa, lips, tongue, fingers, and shoulders. The dental intervention performed on most of these patients is multiple tooth extraction to prevent serious secondary lesions. Objective: To present a clinical case of LNS and describe pediatric dentistry management in patients with self-mutilating behavior. Clinical case: Male patient, 7 years old, LNS carrier. He was referred to the Dental Unit from the Department of Pediatric Neurology for evaluation and management of self-inflicted wounds on fingers, lips and cheeks associated with weight loss and decreased food intake. The surgical procedure consisted of multiple extractions, surgical remodeling of the residual alveolar ridges under general anesthesia. In the second postoperative month, the patient was discharged definitively, with an adequate nutritional status and no signs of self-mutilation in hands or oral cavity. Conclusions: Although LNS is rare, it is essential to know how to proceed in order to provide the best quality of life for patients and their families. Early tooth extractions, as an initial phase in severe cases, seem to be the most useful alternative to minimize damage.

A Case of Lesch-Nyhan Syndrome Manifesting Only Chronic Gouty Arthritis without Neurologic Symptom

Deficiency of hypoxanthine-guanine phosphoribosyltransferase is a purine nucleotide disorder and is the most common genetic cause of uric acid overproduction. This disease has a wide range of spectrum with regard to neurological features depending on the extent of the enzymatic deficiency. Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase, called Lesch-Nyhan syndrome, is presented with hyperuricemia and characteristic neurological manifestation and self-mutilation. Partial hypoxanthine-guanine phosphoribosyltransferase--deficient patients are presented with a various intensities of the aforementioned symptoms, from almost normal neurologic manifestation to a severe form along with hyperuricemia. We report a twenty-year-old man with complete hypoxanthine-guanine phosphoribosyltransferase mutation and Lesch-Nyhan sydrome, who manifested gouty arthritis without neurologic symptom.

Síndrome de Lesch-Nyhan, reporte de un caso clínico / Lesch-Nyhan syndrome, report of a case

El síndrome de Lesch Nyhan es una rara patología cuya incidencia es de 1/380 000 de los nacimientos vivos y en cuyas principales manifestaciones aparecen entre los 3 y 6 meses de edad, y se debe a un error congénito del metabolismo de las purinas, que es causado por una mutación del gen estructural ubicado en el cromosoma X, que determina un déficit de la enzima hipoxantina-guanina-fosforribosil-transferasa. Esta enzima no permite la conversión de la hipoxantina a inosina, lo que hace que el nivel de ácido úrico se eleve más de lo normal afectando principalmente al cerebro y riñones; provocando los trastornos que desarrollan este síndrome. Presentamos el caso clínico de un niño de siete años de edad, con diagnóstico de síndrome de Lesch Nyhan, con características de constantes lesiones autoinflingidas como ser mordedura en la lengua, labios, carrillos y dedos de las manos, acompañado de tofos y trastornos óseos en los miembros inferiores consecuencia del ácido úrico elevado. Para este síndrome no existe tratamiento específico, sólo paliativo.

Lesch Nyhan syndrome is a rare disease whose incidence is 1/380 000 of live births and whose main manifestations appear between 3 and 6 months of age, and is due to an inborn error of purine metabolism, which is caused by a mutation of the structural gene located on the X chromosome, which determines a deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase. This enzyme does not allow the conversion of hypoxanthine to inosine, which causes uric acid level rises above normal mainly affecting the brain and kidneys, causing disorders that develop this syndrome. We report a case of a seven year old, diagnosed with Lesch Nyhan syndrome, with features such as self-inflicted injuries consistent bite on the tongue, lips, cheeks and fingers, accompanied by tophi and bone disorders in accordingly lower limbs elevated uric acid. For this syndrome no specific treatment, only palliative.

Hemicoreoatetosis por hemorragia talámica (Síndrome de Dejérine-Roussy) / Hemichoreoatethosis due to thalamic hemorrhage (Dejérine-Roussy syndrome)

Se trata de una paciente con antecedentes de hipertensión arterial que presentó súbitamente un déficit motor y sensitivo en el hemicuerpo izquierdo por lo que fue hospitalizada y se le halló una hemorragia en el tálamo derecho. Presentó movimientos coreoatetósicos en dicho hemicuerpo, trastornos del comportamiento y de la conducta así como ánimo depresivo. Un año más tarde, solo se consiguió alivio parcial de la coreoatetosis.

A woman patient with past history of arterial hypertension developed right hemihypoestesia and hemiplegia. She was hospitalized and a thalamic hemorrhage was found. Then, she presented hemicoreoathetosis, behavior alterations and depressive mood. One year later, a partial amelioration of choreoathetosis was obtained.

Manifestaciones neurológicas atípicas del síndrome de reconstitución inmunológico por infección con el virus de inmunodeficiencia humana, reporte de los casos / Atypical neurological manifestations of immunologic reconstitution syndrome in the context of HIV infection, a report of two case studies

El síndrome inflamatorio de reconstitución inmunológica en caso de infección por el virus de inmunodeficiencia humana (VIH) es una entidad clínica rara, que se manifiesta con la activación de procesos infecciosos oportunistas que se encontraban estables. Presentamos dos casos de este síndrome con compromiso del sistema nervioso central: síndrome de movimientos anormales y periférico, y síndrome de Guillain Barré...

Immune reconstitution inflammatory syndrome in the context of severe immunosupression secondary to human immunodeficiency virus (HIV) is a clinical entity manifested by a paradoxical clinical impairment due to an activation of infectious opportunistic processes previously under immune surveillance. We illustrate two case reports of immune reconstitution inflammatory syndrome with atypical central nervous system involvement (choreoathetosis) and acute inflammatory demyelinating polineuropathy (Guillain-Barré syndrome)...

A Case of Lesch-Nyhan Disease Manifesting Gouty Arthritis without Self-mutilation / 대한신장학회지

Lesch-Nyhan disease is a very rare X-linked recessive disorder characterized by mental retardation, spasticity resembling cerebral palsy, choreoathetosis, self-mutilation and hyperuricemia. Self-mutilative behavior is a hallmark of the disease. The underlying defect is a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). We report on a fourteen-year-old boy, who manifested gouty arthritis and mild renal insufficiency with Lesch-Nyhan disease, lacking self-mutilative behavior in spite of undetectable HPRT activity. Though there were several reports about some cases of Lesch-Nyhan disease in the past Korean literature, the cases were classic forms with definite neurological manifestation. As far as we know, this is the first case of Lesch-Nyhan disease without self-mutilation in Korea.

General Anesthesia for Extracorporeal Shockwave Lithotripsyin Child with Lesch-Nyhan Syndrome / 영남의대학술지

Lesch-Nyhan syndrome is an inborn error of purine metabolism resulting from hypoxanthine-guanine-phosphoribosyltransferase (HGPRT) deficiency and leading to excess purine production and uric acid over-production. It is a very rare X-linked recessive disorder, characterized by movement disorder, cognitive deficits, and self-injurious behavior. However, because of the high incidence of calculi, patients may present for surgery of urinary tract, and have increased risk of difficult intubation, aspiration pneumonia, renal insufficiency or sudden death. We report the case of a 5-year-old boy with Lesch-Nyhan syndrome who underwent successive extracorporeal shockwave lithotripsy under general anesthesia.

Anesthetic Experience of Percutaneous Nephrolithotomy for Renal Calculi in a Patient with Lesch-Nyhan Syndrome: A case report / 대한마취과학회지

Lesch-Nyhan syndrome (LNS) is a rare, X-linked recessive inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine-phophoribosyltransferase, leading to excessive purine production and elevation of uric acid. Clinical manifestations include mental retardation, spasticity, choreathetosis, compulsive self-mutilation, renal calculi followed by obstructive nephropathy, and arthritis. Patient with LNS may have increased risk of aspiration pneumonia, acute renal failure and unexpected sudden death. We accomplished successful general anesthesia in a case of LNS requiring percutaneous nephrolithotomy due to renal calculi.

Determinación de las constantes cinéticas de la enzima hipoxantina - guanina fosforribosiltransferasa (HGPRT) en controles normales y en una familia afectada por el Sindrome de Lesch-Nyhan / Determination of the Kinetic constants of hypoxanthine guanine phosphoribosyl transférase enzyme (HGPRT) in normal controls and in a family affected by Lesch-Nyhan’s syndrome

El sindrome de Lesch-Nyhan (SLN) es producido por una deficiencia total de la enzima Hipoxantina-Guanina fosforribosiltransferasa (HGPRT). Las madres de niños afectados por el SLN son heterocigotas obligadas ya que la enfermedad se hereda de forma recesiva ligada al cromosoma X. Una de las células utilizadas para determinar la enfermedad es el eritrocito; sin embargo, la determinación de la condición portadora de las madres con niños afectados no se puede hacer en estas células ya que presentan una actividad que cae dentro del rango considerado normal.Esto sucede porque el eritrocito deficiente en la enzima HGPRT es destruido antes de que alcance la circulación sanguínea. Aplicando los principios cinéticos de Lineweaver-Burk y mediante espectrofotometría se determino la cinética de la (HGPRT) extraída de los eritrocitos de una familia que sufre el Sindrome de Lesch-Nyhan y se compararon con la cinética de esta enzima utilizando eritrocitos de 10 individuos sanos y normales procesados de igual forma. Los dos sustratos estudiados fueron la Guanina y el Fosforribosilpirofosfato (PRPP). La Guanina en individuos normales presentó un rango de Vmax entre 1.7 a 2.8 μmol de GMP/ min/ g Hb. mientras que el rango presentado para la Km fue de 10 a 25 μM. El PRPP en los controles normales presentó un rango para la Vmax de 2 a 2.7 μmol de GMP/min/g Hb y el rango para la Km fue de 301 a 590 μM. estos valores corresponden a lo reportado por otros autores. En la familia estudiada la cual tiene dos niños que padecen el síndrome de Lesch- Nyhan, tanto el padre como la hija presentaron cinéticas que caen dentro del rango considerado normal, mientras que la madre presentó una alteración en la Km para el PRPP ( 1176 μ M ). Cuando se comparó la regresión linear de las pendientes presentadas por los controles con la presentada por la paciente portadora de la enfermedad se encontró que estadísticamente son muy diferentes, diferencia que es ocasionada por el valor elevado de la Km de esta paciente por el sustrato PRPP.

The syndrome of Lesch-Nyhan (SLN) is produced by total deficiency of the enzyme Hipoxanthine-Guanine Phosphoribosyltransferase (HGPRT). The mothers of children affected by the SLN are obliged heterocigotes since the illness is inherited from a recessive way bound to the chromosome X. One of the utilized cells to diagnostic the illness is the erythrocyte; however, the determination of the condition carrier of the mothers with affected children cannot make in these cells since they present an activity that falls inside the normal considered range. This happens because the faulty erythrocyte in the enzyme HGPRT is destroyed before it reaches the blood stream. Applying the kinetic principles of Lineweaver-Burk and by means of espectrophotometry I to carry out the kinetic of the HGPRT enzyme extracted of the erythrocytes of a family that it suffers the SLN and they were compared with the kinetics of this enzyme in erythrocytes of ten individuals health and normal. The two studied substrates were the Guanine and the phosphorybosylpirophosphate(PRPP). The Guanine in normal individuals presented a range of Vmax among 1.7 at 2.8 μmol GMP/min/gHb, while the range presented for the Km went from 10 to 25 μ M. The PRPP in the normal controls presented a range for the Vmax from 2 at 2.7μmol GMP/min/gHb and the range for the Km went from 301 to 590 μM. These ranges are similar to those reported by other authors. In the estudied family which has two children that suffer the SLN , as much the father as the daughter presented kinetic that fall inside the normal considered range, while the mother presented increased the km for the PRPP ( the value of Km for the PRPP of the mother of the children affected by the syndrome was of 1176 μ M. When we compared the pendent the normal controls with the obliged heterocigotes pendent for the PRPP substrate was statisticaly different owing to high Km value.

Three Cases of Lesch-Nyhan Syndrome: Cases report

Lesch-Nyhan syndrome is a rare X-linked recessive metabolic disorder characterized by developmental delay, hyperuricemia, choreoathetosis, spasticity, mental retardation, and compulsive self-injurious behavior. This disorder results from a complete deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This syndrome is often misdiagnosed to cerebral palsy and clinical manifestations are usually related to the degree of enzyme deficiency. Complete HGPRT deficiency presents with severe specific neurologic manifestation and nephrolithiasis leading to fatal kidney damage. This report highlighted the importance of clinical awareness leading to early diagnosis and therapy for prevention of the self mutilation and renal failure, even if we couldn't inhibit the progression of neuro-psychotic symptoms.

Lesch-Nyhan syndrome and purine and pyrimidine metabolism didorders / 한양의대학술지

Purine & pyrimidine nucleotides are basic constituents of cellular DNA and RNA polynucleotides. Their function includes regulation of cell metabolism and function, energy conservation and transport and formation of coenzymes and active intermediates of phospholipids and carbohydrate metabolism. The origin of cellular purines and pyrimidines is almost exclusively endogenous source, and the dietary purines play only a minor role. Diagnostic and clinical markers of purine and pyrimidine nucleotide disorders are the level of uric acid, xanthine, hypoxanthine, orotic acid, uracil, thymine, dihydrouracil, dihydrothymine, and succinyladenosine. Clinical manifestations of purine and pyrimidine metabolic disorders are crystalluria and acute renal failure, infections, failure to thrive, and anemia. One of purine metabolic disorders, Lesch-Nyhan disease, is X-linked recessive disorder, presenting motor delay, cerebral palsy, involuntary movements, self-injurious behavior, hyperurcemia, uricosuria, urinary calculi and gouty arthritis. Hypoxanthine-guanine phosphoribosyl transferase(HPRT) is deficient.

Partial HPRT Deficiency Due to a Missense Mutation in the HPRT Gene

An 8-month-old male infant presented with persistent, gross, orange-colored crystals in his urine. His physical and neurological development was normal. Laboratory study showed hyperuricemia, hyperuricosuria and urate crystaluria. He was determined to have partial hypoxanthine-guanine phosphoribosyl transferase(HPRT) deficiency. The molecular genetic analysis revealed a missense mutation in the patient's HPRT gene. By sequencing the patient's cDNA, we identified an A-to-G transition at nucleotide 239, resulting in the replacement of Aspartate with Glycine at amino acid 80 in the HPRT. To our knowledge, this mutation has not previously been reported. Our patient is now being placed on allopurinol therapy, and has had no problem since. Partial HPRT deficiency has been known to cause recurrent acute renal failure without the phenotypic features of Lesch-Nyhan syndrome. Therefore, we think that early diagnosis and treatment are very crucial in preventing acute renal failure.

A Case of Lesch-Nyhan Syndrome

Lesch-Nyhan syndrome is an X-linked recessive disorder characterized by hyperuricemia, choreoathetosis, spasticity, mental retardation, and compulsive, self-injurious behavior. This disorder results from a complete deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyl transferase(HPRT). We report here on a case of Lesch-Nyhan syndrome in a 1-year, 7-month-old male who presented with frequent vomiting, failure to thrive, and developmental delay. The diagnostic work-up revealed hyperuricemia, hyperuricosuria, and medullary nephrolithiasis. The HPRT activity in the erythrocytes was undetectable with a biochemical assay. We also identified de novo mutation which was a deletion of the 649th base, adenosine, in HPRT gene(649delA) by analysis of cDNA using RT-PCR technique coupled with direct sequencing.

Congenital insensitivity to pain (hereditary sensory and autonomic neuropathy) HSAN: a report of two cases.

Pain is one of the protective phenomenon possessed by the body. Pain arouses and demands our immediate attention. There are instances in which there is a congenital insensitivity to pain. Two cases of congenital insensitivity to pain are reported.

Variación de los parametros de laboratorio en pacientes con manejo paralisis tumoral en leucemias agudas - mayo de 2001 / Variations of laboratory parameters in patient with management paralysis tumor in leukemias sharp - May of 2001

Objetivo: Determinar la variación de los parámetros de laboratorio en pacientes con manejo para síndrome de lisis tumoral en leucemias agudas durante la etapa de inducción: Métodos: revisión retrospectiva de los pacientes con leucemias agudas N igual 1443 ingresados en los protocolos de tratamiento en el Instituto de Enfermedades Neoplásicas Dr. Eduardo Cáceres Graziani de enero 1995 a diciembre 1999. El tratamiento y prevención de la lisis tumoral se basaron en normas previamente aprobada. Todos los pacientes recibieron como primer tratamiento manejo para el síndrome de lisis tumoral y dosis de quimioterapia Resultados: n - 168 (9 por ciento) presentaron lisis tumoral, n = 74 (44 por ciento) al diagnostico, n igual 72 (43 por ciento) al inicio del tratamiento y n igual 22 (13 por ciento) durante la fase de inducción. Las variaciones de laboratorio que se observaron al ingreso son: hiperuricemia en n igual 71 (42 por ciento) siendo sus valores más altos al ingreso, tendiendo a normalizarse en los días subsiguientes N igual 6 (3.6 por ciento) presentaron hiperkalemia e hiperfosfatemia N igual 90 (53 por ciento) siendo la alteración más frecuente, observándose incremento luego de iniciado el tratamiento en n igual 106 (63 por ciento); n igual 20(12 por ciento) presentaron hipocalcemia (no se reportaron casos de tetania). En n = 34 (20 por ciento) se detectó elevación de la creatinina al ingreso. No se realizo hemodiálisis en el grupo de pacientes estudiados. Solo se esta estudiando la fase de inducción al tratamiento por ello se reportan defunciones en este estudio.

Ulcera factícia ou auto-induzida: apresentaçäo de um caso clínico / Factitious injury or self-inflicted: a case report

A úlcera factícia da mucosa bucal é uma lesäo ulcerada, de natureza traumática e evoluçäo crônica, geralmente associada a uma condiçäo psiquiátrica e, muitas vezes, de difícil diagnóstico. Os autores relatam o caso de um paciente portador de extensa úlcera factícia comprometendo a face ventro-lateral da língua

Uma nova estratégia para o diagnóstico de mulheres portadoras de mutações que causam a síndrome de LESCH-NYHAN

A síndrome de Lesch-Nyhan é uma entidade clínica que apresenta um padrão de herança recessivo ligado ao cromossomo X. Pertence ao grupo dos erros inatos do metabolismo e é originada por uma deficiência absoluta da enzima hipoxantina-guanina fosforibosiltransferase (HPRT1; EC 2.4.2.8). Mulheres heterozigotas para mutações HPRT1 que causam a síndrome de Lesch-Nyhan podem ser detectadas mediante análises moleculares de híbridos celulares somáticos derivados da fusão de Iinfócitos de sangue periférico e células Hprt-negativas provenientes de roedor com a subseqüente seleção em meio de cultura contendo hipoxantina, aminopterina e timidina (HAT). A origem parental do cromossomo X contendo o alelo HPRT1 normal em linhagens celulares híbridas HPRT1 + pode ser determinada por haplótipos moleculares demonstrados por marcadores altamente polimórficos ligados ao cromossomo X. Esta metodologia foi utilizada para estudar uma possível heterozigota cujo cromossomo X paterno ativo esta sempre presente nas linhagens celulares derivadas dela. Contrariamente, o cromossomo X materno esteve sistematicamente ausente na maioria dos híbridos, e quando presente, estava inativo coexistindo com um X paterno ativo. Sub-clones sem o X paterno ativo e contendo o X materno inativo, não apresentaram atividade HPRT1 quando tratados com 5-aza-citidina. A ausência de transcrito do HPRT1 após o tratamento foi comprovada mediante RT-PCR. Estes resultados claramente demonstraram que a probanda é portadora de uma mutação responsável pela deficiência de HPRT1

Lesch-Nyhan syndrome is a recessive X-Iinked metabolic disorder resulting from absolute deficiency of the enzyme hypoxanthine/guanine phosphoribosy/transferase (HPRT1; EC 2.4.2.8). Heterozygous carriers of HPRT1 mutations responsible for Lesch-Nyhan syndrome can be detected by analysis of somatic cell hybrids derived from peripheral blood Iymphocytes and Hprt-negative cells of rodent origin followed by selection in culture medium containing hypoxanthine, aminopterine, and thymidine (HAT). The parental origin of the X chromosome containing the normal HPRT1 allele in HPRT1 + hybrid cell lines can be determined by molecular haplotyping attributable to highly polymorphic X-Iinked markers. We used this procedure to study a presumed carrier whose paternal active X chromosome always segregated in the cell hybrids derived from her. Conversely, her maternal X chromosome was systematically absent in most of cell hybrids, or when present, it was inactive and coexisted with an active, paternal X chromosome. Sub-clones lacking the paternal, active X chromosome and containing the X inactive maternal chromosome were unable to reactivate the HPRT1 locus following treatment with 5-aza-eytidine. HPRT1 transcripts were found to be absent with RT -PCR. These results c1early demonstrated that the proband was a heterozygous carrier of a mutation responsible for HPRT1 deficiency