The H syndrome: Two novel mutations affecting the same amino acid residue of hENT3

Abstract

H syndrome (OMIM 612391) is a recently described autosomal-recessive genodermatosis with systemic manifestations. The disease is characterized by the major clinical findings of progressive cutaneous hyperpigmentation and hypertrichosis located mainly over the lower limbs and lower abdomen, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height and hyperglycemia/diabetes mellitus [1] and [2]. The major histopathological findings include dermal infiltrate consisting mainly of histiocytes, later replaced by dermal and subcutaneous fibrosis [3]. Recently, we [2] and others [4] found that missense, nonsense, compound and deletion mutations in the SLC29A3 gene are responsible for this unique clinical picture. The SLC29A3 gene encodes the human equilibrative nucleoside transporter (hENT3), which mediates passive sodium-independent transport of nucleosides [5]. The exact cellular localization of hENT3, endosomal/lysosomal [6] or mitochondrial [7], and its function with relation to the H syndrome is still unclear. Here, we report two new cases of H syndrome, of Spanish and of Arab origin and describe two novel missense mutations.