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siklar, zeynep/0000-0003-0921-2694; ABALI, SAYGIN/0000-0001-6552-2801; Turan, Serap/0000-0002-5172-5402; UCAKTURK, Seyit Ahmet/0000-0001-8666-4454; yesiltepe mutlu, gul/0000-0003-3919-7763; Demir, Korcan/0000-0002-8334-2422; Hatun, Sukru/0000-0003-1633-9570 WOS: 000487006600007 PubMed: 31099079 Aims To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. Methods A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. Results After exclusion of the children with a BMI Z-score < 1 SD, those with genetic syndromes associated with Type 2 diabetes, and those whose C-peptide and/or insulin levels were not available, 227 cases were included in the study. Mean age was 13.8 +/- 2.2 (range 6.5-17.8) years, with female preponderance (68%). Family history of Type 2 diabetes was positive in 86% of the children. The mean BMI was 31.3 +/- 6.5 kg/m(2) (range 18.7-61) and BMI Z-score was 2.4 +/- 0.8 (range 1-5). More than half (57%) of the children were identified by an opportunistic diabetes screening due to existing risk markers without typical symptoms of diabetes. Only 13% (n = 29) were treated solely by lifestyle modification, while 40.5% (n = 92) were treated with metformin, 13% (n = 30) were treated with insulin, and 33.5% (n = 76) were treated with a combination of insulin and metformin initially. Mean HbA(1C) levels of the insulin and combination of insulin and metformin groups were 98 (11.1%) and 102 mmol/mol (11.5%), respectively, and also were significantly higher than the lifestyle modification only and metformin groups mean HbA(1C) levels (70(8.6%) and 67 mmol/mol (8.3%), respectively). Conclusions An opportunistic screening of children who are at high risk of Type 2 diabetes is essential, as our data showed that > 50% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists.

A novel heterozygous IVS11-2A>C(c.1957-2A>C) mutation in the GLI2 gene is reported. There was an extremely distinct phenotypical expression in two siblings and their father. The index case was a boy who developed cholestasis and hypoglycaemia in the neonatal period. He had bilateral postaxial polydactyly, mid-facial hypoplasia, high palatal arch, micropenis, and bilateral cryptorchidism. Laboratory examination revealed a diagnosis of multiple pituitary hormone deficiency. There was severe anterior pituitary hypoplasia, absent pituitary stalk and ectopic posterior pituitary on magnetic resonance imaging which suggested pituitary stalk interruption syndrome with no other midline structural abnormality. Molecular genetic analysis revealed a novel heterozygous splicing IVS11-2A>C(c.1957-2A>C) mutation detected in the GLI2 gene. His father and a six-year-old brother with the identical mutation also had unilateral postaxial polydactyly and mid-facial hypoplasia although there was no pituitary hormone deficiency. This novel heterozygous GLI2 mutation detected appears to present with an extremely variable clinical phenotype, even in related individuals with an identical mutation, suggesting incomplete penetrance of this GLI2 mutation.

WOS: 000485922401062 …

Resumen del trabajo presentado a la XI Reunión Anual CIBERER, celebrada en Castelldefels, Barcelona del 12 al 14 de marzo de 2018., Los factores transcripcionales GLI1, GLI2 y GLI3 actúan en el desarrollo embrionario como mediadores de los morfógenos Hedgehog (Hh). En consecuencia, variantes deletéreas en GLI2 y GLI3 han sido reportadas como responsables de defectos congénitos. Sin embargo, hasta la fecha no se habían descrito mutaciones en GLI1, por lo que el papel de este gen en el desarrollo humano permanecía desconocido. Aquí presentamos 8 pacientes de tres familias distintas con mutaciones en GLI1 y características clínicas similares a las del Síndrome de Ellis-van Creveld (EvC), una enfermedad causada por la disminución de la actividad de la vía de Hh. Dos familias portaban mutaciones de fin de mensaje en el último exón del gen y la tercera un codón de parada en la región N-terminal. El análisis de fibroblastos de uno de los pacientes con mutaciones en el último exón demostró que las células de este paciente sintetizan la proteína truncada correspondiente e inducen su expresión en respuesta a un agonista químico de Hh. Sin embargo, ensayos “in vivo” y en cultivo celular revelaron que la actividad transcripcional de la proteína mutante se encontraba drásticamente disminuida. Consistentemente, las células del paciente presentaron menor expresión de la diana de Hh, PTCH1. Este trabajo muestra que la inactivación de GLI1 da lugar a alteraciones del desarrollo que varían desde polidactilia postaxial aislada hasta fenotipos solapantes con EvC, a la vez que pone de manifiesto que todos los miembros de la triada GLI son necesarios en el desarrollo humano.

WOS: 000451667000012, PubMed ID: 29553041, Aromatase deficiency is a rare autosomal recessive genetic disorder with an unknown incidence. Aromatase converts androgens into estrogen in the gonadal and extra-gonadal tissues. Aromatase deficiency causes ambiguous genitalia in the Female fetus and maternal virilization (hirsutism, acne, cliteromegaly, deep voice) during pregnancy due to increased concentration of androgens. A 19 months old girl patient was assessed due to presence of ambiguous genitalia. There were findings of maternal virilization during pregnancy. The karyotype was 46,XX. Congenital adrenal hyperplasia was not considered since adrenocorticotropic hormone, cortisol, and 17-hydroxyprogesterone levels were within normal ranges. At age two months, follicle-stimulating hormone and total testosterone levels were elevated and estradiol level was low. Based on these findings, aromatase deficiency was suspected. A novel homozygous mutation IVS7-2A > G (c.744-2A >G) was identified in the CYP19A1 gene. Pelvic ultrasound showed hypoplasic ovaries rather than large and cystic ovaries. We identified a novel mutation in the CYP19A1 gene in a patient who presented with ambiguous genitalia and maternal virilization during pregnancy. Presence of large and cystic ovaries is not essential in aromatase deficiency.