Significance of genetic testing for paternal uniparental disomy of chromosome 6 in neonatal diabetes mellitus☆,☆☆
Section snippets
Patient 1
A male infant was born by cesarean section at 36 weeks’ gestation to a 39-year-old woman (gravida 4, para 3, abortion 1) of mixed European descent. The father was 5’9” tall and the mother 5’1”. The mother did not have gestational diabetes and had no family history of diabetes. Because of advanced maternal age, amniocentesis was performed and revealed a normal 46,XY male karyotype. Pregnancy was complicated by poor growth from 28 weeks and oligohydramnios. Apgar scores were 9 and 9 at 1 and 5
METHODS
For DNA polymorphism analysis, blood samples were obtained from each patient and both parents. Whole-cell lysates were prepared from peripheral blood by using the QIAamp blood lysis kit (Qiagen Inc, Santa Clarita, Calif). Microsatellite markers were selected based on their localization along chromosome 6, and primer pairs were acquired from Research Genetics (Huntsville, Ala).
The polymerase chain reactions were set up in a total volume of 10 μL. The reaction mixture contained 10 mmol/L Tris-HCl
RESULTS
The results of the DNA polymorphism analysis, with microsatellite markers extending along the length of chromosome 6, are presented in the Table for each patient and both parents. Patient 1 shows inheritance of a single paternal allele for 13 informative markers of 16 studied (Table, Fig 2).
DISCUSSION
NDM is a rare condition usually observed in conjunction with IUGR.10 In those cases with TNDM, only 18% of patients required insulin for more than 6 months, and the longest observed duration has been 18 months.11 Approximately one third to one half of the patients proved to have PNDM.1, 12, 13
Macroglossia in an infant with TNDM and IUGR was initially described by Dacou-Voutetakis et al14 in 1975. These authors identified 2 additional cases in the literature3, 15 and suggested that TNDM, IUGR,
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Neonatal hyperglycaemia and abnormal development of the pancreas
2008, Best Practice and Research in Clinical Endocrinology and MetabolismCitation Excerpt :TNDM is usually sporadic, but paternal transmission has been documented in about one third of reported patients, some of whom had non-diabetic fathers.1,11 Paternal isodisomy of chromosome 6 has been demonstrated in several unrelated patients with TNDM (Figure 1).6,12 Other patients had partial duplications of the long arm of the paternal chromosome 6.13,14
Neonatal and very-early-onset diabetes mellitus
2004, Seminars in NeonatologyNeonatal diabetes mellitus: Chromosomal analysis in transient and permanent cases
2002, Journal of PediatricsCitation Excerpt :As previously described,31 no phenotype differences were found between the 3 subsets defined on the basis of the chromosome 6 abnormality, but this may be because of the small number of patients in each of these subsets. Our findings in a considerably larger group of patients than in previous publications provide additional strong evidence that chromosome 6 abnormalities are associated with TNDM as opposed to PNDM.10,35 Genetic counseling can be offered to patients with TNDM and a chromosome 6 abnormality.
Insulin-dependant neonatal and infant diabetes: Genetics and physiopathology
2002, Pathologie BiologieHuman chromosome variation: Heteromorphism, polymorphism and pathogenesis: Second edition
2017, Human Chromosome Variation: Heteromorphism, Polymorphism and Pathogenesis: Second EditionApplication of chromosome microarray analysis for prenatal diagnosis of a fetus with partial duplication of lp and uniparental disomy of chromosome 6
2015, Chinese Journal of Medical Genetics
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Reprint requests: David H. Ledbetter, PhD, Department of Human Genetics, The University of Chicago, 924 East 57th St, Chicago, IL 60637.
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