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OBJECTIVE Transient neonatal diabetes mellitus 1 (TNDM1) is the most common cause of diabetes presenting at birth. Approximately 5% of the cases are due to recessive ZFP57 mutations, causing hypomethylation at the TNDM locus and other imprinted loci (HIL). This has consequences for patient care because it has impact on the phenotype and recurrence risk for families. We have determined the genotype, phenotype, and epigenotype of the first 10 families to alert health professionals to this newly described genetic subgroup of diabetes. RESEARCH DESIGN AND METHODS The 10 families (14 homozygous/compound heterozygous individuals) with ZFP57 mutations were ascertained through TNDM1 diagnostic testing. ZFP57 was sequenced in probands and their relatives, and the methylation levels at multiple maternally and paternally imprinted loci were determined. Medical and family histories were obtained, and clinical examination was performed. RESULTS The key clinical features in probands were transient neonatal diabetes, intrauterine growth retardation, macroglossia, heart defects, and developmental delay. However, the finding of two homozygous relatives without diabetes and normal intelligence showed that the phenotype could be very variable. The epigenotype always included total loss of methylation at the TNDM1 locus and reproducible combinations of differential hypomethylation at other maternally imprinted loci, including tissue mosaicism. CONCLUSIONS There is yet no clear genotype–epigenotype–phenotype correlation to explain the variable clinical presentation, and this results in difficulties predicting the prognosis of affected individuals. However, many cases have a more severe phenotype than seen in other causes of TNDM1. Further cases and global epigenetic testing are needed to clarify this.

OBJECTIVE: According to the classical knowledge risk of respiratory distress more often in neonates who were born by ceserean delivery. The purpose of this study was to determine whether respiratory distres is associated with ceserean delivery, gestation week and sex of neonate. Study Design: We noted delivery type, gestational age and sex of all newborn's who were delivered after 37 gestation weeks and born in VKV Amerikan Hospital between years 1998-2005. We reached the data of babies who developed respiratory distress from NICU database. RESULTS: In this 8 years period 1101 vajinal delivery (15%),6243 ceserean delivery (85%) were occured of total 7344 babies. Sex of babies were 3613 female (%49), 3731 male (51%). 72 of babies developed respiratory distres (0.9%), 5 of them were delivered vajinal (0.4%) 67 were delivered by ceserean (0.9%) (p=0.054). 61 of these babies developed transient tachypnea of the newborn (TTN) (0.8%) and 11 developed respiratory distress syndrome(RDS) (0.1%). 5 babies were delivered vaginally, 56 babies were delivered by ceserean of 61who developed TTN ( p=0.13). All 11 babies were delivered by ceserean who were developed RDS. 63% of RDS (7/11) were male (p=0.39). 83% of TTN (51/61) were male (p=0.0001). Who developed respiratory distress (TTN+RDS) were male 80%. 4 of 11 babies with RDS were born at 37th gestational week (36%), 7 were born 38 and after 38 gestational weeks. 17 of 61 babies with TTN were born at 37th gestational week (27%) 44 were born 38 and after gestational weeks. CONCLUSIONS: In this study we found respiratory distress ratio %0.9 as known 1% in classical literature knowledge. But contrary to classical knowledge there were no statistically differences between vaginal and ceserean deliveries for developing respiratory distress. But in male newborns respiratory distress ratio was higher than females.

OBJECTIVE Transient neonatal diabetes mellitus 1 (TNDM1) is the most common cause of diabetes presenting at birth. Approximately 5% of the cases are due to recessive ZFP57 mutations, causing hypomethylation at the TNDM locus and other imprinted loci (HIL). This has consequences for patient care because it has impact on the phenotype and recurrence risk for families. We have determined the genotype, phenotype, and epigenotype of the first 10 families to alert health professionals to this newly described genetic subgroup of diabetes. RESEARCH DESIGN AND METHODS The 10 families (14 homozygous/compound heterozygous individuals) with ZFP57 mutations were ascertained through TNDM1 diagnostic testing. ZFP57 was sequenced in probands and their relatives, and the methylation levels at multiple maternally and paternally imprinted loci were determined. Medical and family histories were obtained, and clinical examination was performed. RESULTS The key clinical features in probands were transient neonatal diabetes, intrauterine growth retardation, macroglossia, heart defects, and developmental delay. However, the finding of two homozygous relatives without diabetes and normal intelligence showed that the phenotype could be very variable. The epigenotype always included total loss of methylation at the TNDM1 locus and reproducible combinations of differential hypomethylation at other maternally imprinted loci, including tissue mosaicism. CONCLUSIONS There is yet no clear genotype–epigenotype–phenotype correlation to explain the variable clinical presentation, and this results in difficulties predicting the prognosis of affected individuals. However, many cases have a more severe phenotype than seen in other causes of TNDM1. Further cases and global epigenetic testing are needed to clarify this.

We have previously described individuals presenting with transient neonatal diabetes and showing a variable pattern of DNA hypomethylation at imprinted loci throughout the genome. We now report mutations in ZFP57, which encodes a zinc-finger transcription factor expressed in early development, in seven pedigrees with a shared pattern of mosaic hypomethylation and a conserved range of clinical features. This is the first description of a heritable global imprinting disorder that is compatible with life.