Lethal proliferation of erythroid precursors in a neonate with a germline PTPN11 mutation

Abstract

We report a neonate with hypertrophic cardiomyopathy and lethal myeloproliferative disorder with excessively proliferating immature erythroid precursors infiltrating non-hematopoietic organs. Mutational analysis uncovered a germline mutation in the Noonan syndrome/LEOPARD syndrome (NS/LS) gene PTPN11. In conclusion, this case report suggests that congenital myeloproliferative disorders in association with germline PTPN11 mutations may affect the erythroid lineage.

Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss

“…The c.1492C > T variant is located in exon 13 which is a hot spot region for this gene. This variant has previously been reported in individuals with LEOPARD syndrome with variable phenotypic features including multiple lentigines, hypertrophic cardiomyopathy, dysmorphic facial features and variable degree of cognitive deficits (Table 3)1314151634.…”

“…We detected heterozygous pathogenic variants in five different SHL genes that can explain HL in five (4.9%) Turkish families (Table 1). The pathogenic variants MITF (MIM 156845) c.328C > T78 (Waardenburg syndrome type II; MIM 193510), SOX10 (Kallmann syndrome) c.481C > T9, CHD7 (MIM 608892) c.5050G > A9101112 (CHARGE syndrome; MIM 214800 and Kallmann syndrome; MIM 612370), PTPN11 (MIM 176876) c.1492C > T13141516 (LEOPARD syndrome; MIM 151100), and KMT2D (MIM 602113) c.13259G > A17 (Kabuki syndrome; MIM 147920) had all been previously reported in patients with syndromic findings. All the identified variants were confirmed with Sanger sequencing in probands and tested for in available family members (Fig.…”

Malignant Diseases in Noonan Syndrome and Related Disorders

“…Most cases resolve spontaneously, but fatal progressive disease has been reported in 3 patients (10% of approximately 30 patients reported) [11,15,16]. Progression to AML occurred in 1 patient at 2 years of age [9].…”

Co‐occurrence of hypertrophic cardiomyopathy and juvenile myelomonocytic leukemia in a neonate with Noonan syndrome, leading to premature death

“…These observations may account for this apparent contradiction of having both HCM and JMML due to p.Thr42Ala mutation in PTPN11 . To the best of our knowledge, two neonates with NS presenting with co‐occurrence of HCM and MPD with p.Thr73Ile and p.Arg498Trp mutations have been reported in the literature 18, 19. However, the co‐occurrence of HCM and JMML in neonates with NS with p.Thr42Ala has not been reported before.…”

“…So far, only two neonates with NS presenting with concurrent HCM and MPD with p.Thr73Ile and p.Arg498Trp have been reported in the literature 18, 19. Furthermore, the co‐occurrence of HCM and JMML in patients with NS leading to premature death has never been reported before.…”