Clinical and genetic findings of five patients with WT1-related disorders

Abstract

Aim: To present phenotypic variability of WT1-related disorders. Methods: Description of clinical and genetic features of fi ve 46,XY patients with WT1 anomalies. Results: Patient 1: newborn with genital ambiguity; he developed Wilms tumor (WT) and chronic renal disease and died at the age of 10 months; the heterozygous 1186G>A mutation compatible with Denys-Drash syndrome was detected in this child. Patients 2 and 3: adolescents with chronic renal disease, primary amenorrhea and hypergonadotrophic hypogonadism; patient 2 had a gonadoblastoma. The heterozygous IVS9+4, C>T mutation, compatible with Frasier syndrome was detected. Patient 4: 9-year-old boy with aniridia, genital ambiguity, dysmorphisms and mental defi ciency; a heterozygous 11p deletion, compatible with WAGR syndrome was detected. Patient 5: 2 months old, same diagnosis of patient 4; he developed WT at the age of 8 months. Conclusions: Constitutional abnormalities of WT1 cause gonadal and renal anomalies and predisposition to neoplasia and must be investigated in patients with ambiguous genitalia, chronic renal disease and(or) Wilms tumors; primary amenorrhea with chronic renal disease; and aniridia, genital ambiguity and dysmorphisms.

Wilms’ Tumour in Young Adult

“…The genes that are commonly affected are WT1 and WT2 corresponding to the gene locus 11p13 and 11p15 respectively. [4,5] The syndromes that are commonly associated are WAGR, Denys-Drash syndrome, Beckwith-Wiedemann syndrome and various others. Recently WTX gene have been found inactivated in onethird of the case mapped to Xq11.1.…”

46,XY-disorder of sex development due to a mutation in the WT1 gene

“…Мутації в даному гені описані при синдромах Деніс-Дреш, WAGR, вродженому нефротичному синдромі, гострому мієлоїдному лейкозі, раку простати [11][12][13].…”

“…Пробанди з каріотипом 46,ХХ зазвичай мають правильно сформовані зовнішні геніталії за жіночим типом і клінічні прояви синдрому стосуються лише нирок (ізольований нефротичний синдром). Тип успадкування синдрому аутосомно-домінантний [12,[14][15][16].…”

Macrosomia and ambiguous genitalia: a long overdue answer to the citizens of Frusino

“…Inadequate biosynthesis of sex steroids can result from various enzymatic deficien-Different mutations by converging on a loss of function of WT1 protein isoforms result in a spectrum of disorders, namely Frasier, Denys-Drash and WAGR syndromes, commonly characterized by renal disease, intersex and predisposition to tumorigenesis. 12 As for genital abnormalities, sexes are not similarly affected. Although 46XY fetuses appear to be male pseudohermaphrodites exhibiting ambiguous genitalia, 46XX fetuses usually appear with a normal phenotype but occasionally with streak gonads.…”

“…Similarly, in 206 BC "at Caere…a lamb had been yeaned which was both male and female" (Livy XXVIII,11,3 2 ). And in 200 BC, "Besides, monstrous births of animals [that] were reported to have occurred in many places, in the country of the Sabines, an infant was born whose sex was doubtful; and another was found, sixteen years old, of doubtful sex" (Livy XXXI,12,4 3 ). Since those irregularities pertaining to the matter of sex were especially discountenanced, the public regarding them as utter abominations, hermaphrodites were drowned in the sea, the element that was said to purify all enormities.…”