Background/aim Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder. Clinical diagnosis is difficult in early childhood, and it is possible to miss a critical interval for tumour screening. In this study, we aimed to characterize the mutational spectrum of Turkish patients and discuss the benefits of molecular testing. Material and methods Fifty individuals from 35 unrelated families were included. Main referral reasons for genetic testing were as follows: to confirm a clinical diagnosis, to use in differential diagnosis and to evaluate first‐degree family member of a known patient. Two‐step process consisting of initial next generation sequencing of the NF1 gene and consequent multiplex ligation‐dependent probe amplification were performed. Results We identified a total of 30 variants in 28 individuals. Variant detection rate was 56% in the entire study group and 71.4% within the index patients. Four novel variants were found. Truncating variants constituted 60% of the entire mutation spectrum. A deletion or duplication was not detected. The most common feature was cafe au lait macules in 70% of the patients, followed by focal areas of signal intensity on brain imaging (26%), cutaneous neurofibromas (24%) and axillary freckling (24%). Conclusions Early sequencing in all suspected patients followed by deletion/duplication analysis in patients meeting clinical criteria and a case‐to‐case based consideration for RNA studies seems to be the effective algorithm for NF‐1 diagnosis.

Tanatoforik displazi (TD), ilk kez 1967 yılında Maroteux ve arkadaşları tarafından tanımlanan, en sık gözlenen konjenital letal iskelet displazisidir (1,2). İnsidansı 1/20.000 ile 1/50.000 arasında bildirilmekle beraber olguların tamamı yeni mutasyon sonucu ortaya çıkan sporadik olgulardır (3,4). Bu olgularda makrosefali, frontal bombeleşme, basık burun kökü, toraks uzunluğunun normal olduğu dar toraks ve kısa kostalar, platispondili, ağır kısa ekstremite cüceliği gibi bulgular gözlenir (5,6). Olguların çoğunda erken postnatal dönemde dar toraksın neden olduğu pulmoner hipoplazi ya da foramen magnum stenozunun neden olduğu solunum yetmezliğinden ölüm gerçekleşir (7). Tanatoforik displazi iki tipe ayrılır. En sık görülen tip 1'de değişken ve genelde hafif düzeyde kraniyosinositoz ve femurlarda eğrilme gözlenirken, tip 2'de kafada yonca yaprağı bulgusu sıklıkla ÖZ Tanatoforik displazi, genelde perinatal dönemde ölümle sonuçlanan ve kısa ekstremiteler ile kendini gösteren yenidoğanın cücelik sendromlarından biridir. Makrosefali, belirgin alın, dar toraks, vertebralarda düzleşme, ekstremitelerde kısalık, femurda eğrilme ile karakterizedir. Fibroblast büyüme faktörü reseptörü 3 (FGFR3) genindeki mutasyonlardan kaynaklanır ve otozomal dominant kalıtım modeli gösterir. Bu makalede, prenatal dönemde anormal USG bulguları olan, amniyosentez materyalinden yapılan FGFR3 gen analizi ile p.R248C mutasyonu saptanan bir olgu anlatılmıştır.Anahtar kelimeler: tanatoforik displazi, fibroblast büyüme faktörü, FGFR3 geni, yenidoğan cüceliği, prenatal tanı ABSTRACT Thanatophoric dysplasia is one of the newborn's dwarfism syndromes usually resulting in death during perinatal period and manifesting as short extremities. It is characterized by macrocephaly, prominent forehead, narrow thorax, short extremities, flattened vertebral bodies, curved femurs. This is caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene and shows autosomal dominant inheritance model. In this report, we presented a case with abnormal USG findings during perinatal period and detected to carry a p.R248C mutation in FGFR3 gene in amniosynthesis fluid.