Genetic diagnosis of one family with incomplete clinical data
-
Shiyan Xu
Abstract
A 6-day-old female patient suddenly died of congestive heart failure, hepatomegaly and hypoglycemic encephalopathy. Tandem mass spectrometry (MS) analysis revealed a possibility of carnitine deficiency. However, many of the clinical symptoms had not yet occurred at that time, and the clinical data was incomplete. We aim to derive a systematic procedure of identifying pathogenic mutations for similar patients. Physicians could save patients’ lives with effective treatment at a much earlier stage. Direct sequencing of the exons and exon–intron boundaries of GAA, SLC25A5, CPT1, CPT2, SLC25A20 and MUT genes were performed on the parents of the patient. DNA from the blood spots of the patient was analyzed for the MUT gene. The results revealed that the patient was a compound heterozygote with MUT. c. 729_730insTT and c. 1677-1G>A. cDNA sequence demonstrated MUT c. 1677-1G>A resulting in the deletion of eight nucleotides and the introduction of 13 novel amino acids before premature termination.
We extend our warm thanks to the patient and relatives, for kindly donating both their time and biological samples to our genetic studies. We also thank the doctors who have provided us with the patient’s information. WYJ was supported by the Chinese National Natural Scientific Grants (No. 31171214 and U1132606).
References
1. Pons R, De Vivo DC. Primary and secondary carnitine deficiency syndromes. J Child Neurol 1995;10(Suppl 2):S8–24.10.1177/0883073895010002S03Suche in Google Scholar
2. Wang F, Han L, Yang Y, Gu X, Ye J, et al. Clinical, biochemical, and molecular analysis of combined methylmalonic acidemia and hyperhomocysteinemia (cblC type) in China 2010. J Inherit Metab Dis 2010;Oct 6 [Epub ahead of print].10.1007/s10545-010-9217-0Suche in Google Scholar
3. Koizumi A, Nozaki J, Ohura T, Kayo T, Wada Y, et al. Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency. Hum Mol Genet 1999;8:2247–54.10.1093/hmg/8.12.2247Suche in Google Scholar
4. Shibbani K, Fahed AC, Al-Shaar L, Arabi M, Nemer G, et al. Primary Carnitine Deficiency: Novel mutations and insights into the cardiac phenotype. Clin Genet 2013;Feb 4 [Epub ahead of print].10.1111/cge.12112Suche in Google Scholar
5. Scaglia F, Longo N. Primary and secondary alterations of neonatal carnitine metabolism. Semin Perinatol 1999;23:152–61.10.1016/S0146-0005(99)80047-0Suche in Google Scholar
6. Frazier DM, Millington DS, McCandless SE, Koeberl DD, Weavil SD, et al. The tandem mass spectrometry newborn screening experience in North Carolina: 1997–2005. J Inherit Metab Dis 2006;29:76–85.10.1007/s10545-006-0228-9Suche in Google Scholar PubMed
7. Dietzen DJ, Rinaldo P, Whitley RJ, Rhead WJ, Hannon WH, et al. National academy of clinical biochemistry laboratory medicine practice guidelines: follow-up testing for metabolic disease identified by expanded newborn screening using tandem mass spectrometry; executive summary. Clin Chem 2009;55:1615–26.10.1373/clinchem.2009.131300Suche in Google Scholar PubMed
8. Oba-Shinjo SM, Da SR, Andrade FG, Palmer RE, Pomponio RJ, et al. Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations. J Neurol 2009;256:1881–90.10.1007/s00415-009-5219-ySuche in Google Scholar PubMed
9. Feng Y, Zheng P, Zhao H, Wu K. SLC22A4 and SLC22A5 gene polymorphisms and Crohn’s disease in the Chinese Han population. J Dig Dis 2009;10:181–7.10.1111/j.1751-2980.2009.00383.xSuche in Google Scholar PubMed
10. Bennett MJ, Boriack RL, Narayan S, Rutledge SL, Raff ML. Novel mutations in CPT 1A define molecular heterogeneity of hepatic carnitine palmitoyltransferase I deficiency. Mol Genet Metab 2004;82:59–63.10.1016/j.ymgme.2004.02.004Suche in Google Scholar PubMed
11. Taggart RT, Smail D, Apolito C, Vladutiu GD. Novel mutations associated with carnitine palmitoyltransferase II deficiency. Hum Mutat 1999;13:210–20.10.1002/(SICI)1098-1004(1999)13:3<210::AID-HUMU5>3.0.CO;2-0Suche in Google Scholar
12. Costa C, Costa JM, Slama A, Boutron A, Vequaud C, et al. Mutational spectrum and DNA-based prenatal diagnosis in carnitine-acylcarnitine translocase deficiency. Mol Genet Metab 2003;78:68–73.10.1016/S1096-7192(02)00205-6Suche in Google Scholar
13. Sakamoto O, Ohura T, Matsubara Y, Takayanagi M, Tsuchiya S. Mutation and haplotype analyses of the MUT gene in Japanese patients with methylmalonic acidemia. J Hum Genet 2007;52:48–55.10.1007/s10038-006-0077-2Suche in Google Scholar
14. Martinez MA, Rincon A, Desviat LR, Merinero B, Ugarte M, et al. Genetic analysis of three genes causing isolated methylmalonic acidemia: identification of 21 novel allelic variants. Mol Genet Metab 2005;84:317–25.10.1016/j.ymgme.2004.11.011Suche in Google Scholar
15. Fowler B, Leonard JV, Baumgartner MR. Causes of and diagnostic approach to methylmalonic acidurias. J Inherit Metab Dis. 2008;31:350–60.10.1007/s10545-008-0839-4Suche in Google Scholar
©2013 by Walter de Gruyter Berlin Boston
Artikel in diesem Heft
- Masthead
- Masthead
- Review article
- Tamoxifen therapy for the management of pubertal gynecomastia: a systematic review
- Images in pediatric endocrinology
- Solitary median maxillary central incisor, a clinical predictor of hypoplastic anterior pituitary, ectopic neurohypophysis and growth hormone deficiency
- A rare case of granuloma annulare in a 6-year-old child with type 1 diabetes
- Original articles
- The arginine stimulation test: timing of peak is not a helpful parameter in the diagnosis of growth hormone deficiency
- The relationship between adiposity and stature in prepubertal children with celiac disease
- Influence of micronutrient status and socioeconomic gradient on growth indices of 2–18-year-old Indian girls
- Phosphotyrosine phosphatases in GH-stimulated skin fibroblasts from children with idiopathic short stature
- The relation between salivary cortisol and the metabolic syndrome score in girls
- Association of vitamin D concentrations with adiposity indices among preadolescent children in Korea
- Association of serum resistin levels with metabolic syndrome and early atherosclerosis in obese Chinese children
- Characteristics of infants at risk of hypoglycaemia secondary to being ‘infant of a diabetic mother’
- Parental dyadic coping in families of children and adolescents with type 1 diabetes
- Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) syndrome is associated with severe chronic inflammation and cardiomyopathy, and represents a new monogenic autoinflammatory syndrome
- Effect of insulin therapy on IGF-1 level in children with new-onset type 1 diabetes mellitus: a comparison between DKA and non-DKA
- Mutation analysis of the SRD5A2, AR and SF-1 genes in 52 Chinese boys with hypospadias
- Sexual development in prepubertal obese boys: a 4-year longitudinal study
- Genetic diagnosis of one family with incomplete clinical data
- Patient reports
- Complete androgen insensitivity syndrome and discordant Müllerian remnants: two cases with novel mutation in the androgen receptor
- Psychosexual outcomes in three siblings with partial androgen insensitivity syndrome: impact of nature versus nurture
- Ambiguous genitalia in a 48, XXYY newborn: a casual relationship or a coincidence?
- Gonadal function of beta-thalassemics following stem cell transplantation conditioned with myeloablative and reduced intensity regimens
- Significant testicular enlargement in a 6.5-year-old boy with monorchism and testicular microlithiasis
- Report of the first case of precocious puberty in Rett syndrome
- Type II vitamin D-dependent rickets with diabetic ketoacidosis
- Pituitary gigantism presenting with depressive mood disorder and diabetic ketoacidosis in an Asian adolescent
- A rare association between Rathke’s cyst and hypophysitis in a patient with delayed sex development and growth failure
- Diabetes mellitus with Laron syndrome: case report
- Wegener granulomatosis as an uncommon cause of panhypopituitarism in childhood
- Rare cases of autoimmune hypothyroidism in young children
- Cushing syndrome related to leukemic infiltration of the central nervous system: a case report and a possible role of LIF
- Early presentation of bilateral gonadoblastomas in a Denys-Drash syndrome patient: a cautionary tale for prophylactic gonadectomy
- Identification of a novel homozygous mutation (S144I) in a Malay patient with maple syrup urine disease
- Virilization in two pre-pubertal children exposed to topical androgen
- A family with Camurati-Engelman disease. The role of the missense p.R218C mutation in TGFB1 in bones and endocrine glands
- Short communications
- Plasma ceramides are elevated in female children and adolescents with type 2 diabetes
- Assessment of contractility and myocardial function in small and appropriate for gestational age premature neonates using the stress-velocity relationship and tissue Doppler imaging immediately after birth
- Letter to the Editors
- Homeostasis model assessment of insulin resistance may not be reliable to evaluate insulin sensitivity in young obese children
- Type 1 diabetes in women with endometriosis: what is the risk of occurrence?
- How should we manage vitamin D-deficient adolescents?
- Should neonatal hyperparathyroidism associated with mucolipidosis II/III be treated pharmacologically?a
Artikel in diesem Heft
- Masthead
- Masthead
- Review article
- Tamoxifen therapy for the management of pubertal gynecomastia: a systematic review
- Images in pediatric endocrinology
- Solitary median maxillary central incisor, a clinical predictor of hypoplastic anterior pituitary, ectopic neurohypophysis and growth hormone deficiency
- A rare case of granuloma annulare in a 6-year-old child with type 1 diabetes
- Original articles
- The arginine stimulation test: timing of peak is not a helpful parameter in the diagnosis of growth hormone deficiency
- The relationship between adiposity and stature in prepubertal children with celiac disease
- Influence of micronutrient status and socioeconomic gradient on growth indices of 2–18-year-old Indian girls
- Phosphotyrosine phosphatases in GH-stimulated skin fibroblasts from children with idiopathic short stature
- The relation between salivary cortisol and the metabolic syndrome score in girls
- Association of vitamin D concentrations with adiposity indices among preadolescent children in Korea
- Association of serum resistin levels with metabolic syndrome and early atherosclerosis in obese Chinese children
- Characteristics of infants at risk of hypoglycaemia secondary to being ‘infant of a diabetic mother’
- Parental dyadic coping in families of children and adolescents with type 1 diabetes
- Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) syndrome is associated with severe chronic inflammation and cardiomyopathy, and represents a new monogenic autoinflammatory syndrome
- Effect of insulin therapy on IGF-1 level in children with new-onset type 1 diabetes mellitus: a comparison between DKA and non-DKA
- Mutation analysis of the SRD5A2, AR and SF-1 genes in 52 Chinese boys with hypospadias
- Sexual development in prepubertal obese boys: a 4-year longitudinal study
- Genetic diagnosis of one family with incomplete clinical data
- Patient reports
- Complete androgen insensitivity syndrome and discordant Müllerian remnants: two cases with novel mutation in the androgen receptor
- Psychosexual outcomes in three siblings with partial androgen insensitivity syndrome: impact of nature versus nurture
- Ambiguous genitalia in a 48, XXYY newborn: a casual relationship or a coincidence?
- Gonadal function of beta-thalassemics following stem cell transplantation conditioned with myeloablative and reduced intensity regimens
- Significant testicular enlargement in a 6.5-year-old boy with monorchism and testicular microlithiasis
- Report of the first case of precocious puberty in Rett syndrome
- Type II vitamin D-dependent rickets with diabetic ketoacidosis
- Pituitary gigantism presenting with depressive mood disorder and diabetic ketoacidosis in an Asian adolescent
- A rare association between Rathke’s cyst and hypophysitis in a patient with delayed sex development and growth failure
- Diabetes mellitus with Laron syndrome: case report
- Wegener granulomatosis as an uncommon cause of panhypopituitarism in childhood
- Rare cases of autoimmune hypothyroidism in young children
- Cushing syndrome related to leukemic infiltration of the central nervous system: a case report and a possible role of LIF
- Early presentation of bilateral gonadoblastomas in a Denys-Drash syndrome patient: a cautionary tale for prophylactic gonadectomy
- Identification of a novel homozygous mutation (S144I) in a Malay patient with maple syrup urine disease
- Virilization in two pre-pubertal children exposed to topical androgen
- A family with Camurati-Engelman disease. The role of the missense p.R218C mutation in TGFB1 in bones and endocrine glands
- Short communications
- Plasma ceramides are elevated in female children and adolescents with type 2 diabetes
- Assessment of contractility and myocardial function in small and appropriate for gestational age premature neonates using the stress-velocity relationship and tissue Doppler imaging immediately after birth
- Letter to the Editors
- Homeostasis model assessment of insulin resistance may not be reliable to evaluate insulin sensitivity in young obese children
- Type 1 diabetes in women with endometriosis: what is the risk of occurrence?
- How should we manage vitamin D-deficient adolescents?
- Should neonatal hyperparathyroidism associated with mucolipidosis II/III be treated pharmacologically?a
