ENPP 1 encodes ectonucleotide pyrophosphatase/phosphodiesterase 1 ( ENPP 1), which is responsible for the generation of inorganic pyrophosphate, a natural inhibitor of mineralization. All mutations were found to affect cysteine residues in the somatomedin-B-like 2 (SMB2) domain in the encoded protein, which has been implicated in insulin signaling. Using a combination of exome and direct sequencing, we showed complete cosegregation of the disease phenotype with three heterozygous ENPP 1 mutations in three unrelated families.
Here, we deciphered the genetic basis of Cole disease, a rare autosomal-dominant genodermatosis featuring punctate keratoderma, patchy hypopigmentation, and uncommonly, cutaneous calcifications. The coexistence of abnormal keratinization and aberrant pigmentation in a number of cornification disorders has long suggested a mechanistic link between these two processes.
Early onset conductive hearing loss may further distinguish the autosomal recessive ENPP 1 related type from other types of hypophosphatemia.Ĭole Disease Results from Mutations in ENPP 1.Įytan, Ori Morice-Picard, Fanny Sarig, Ofer Ezzedine, Khaled Isakov, Ofer Li, Qiaoli Ishida-Yamamoto, Akemi Shomron, Noam Goldsmith, Tomer Fuchs-Telem, Dana Adir, Noam Uitto, Jouni Orlow, Seth J Taieb, Alain Sprecher, Eli This report of two unrelated infants with compound heterozygous mutations in ENPP 1 and previously published cases confirms that mild to moderate hearing loss is frequently associated with ARHR2. Both children had evidence of progressive hearing loss requiring the use of hearing aids. We report two children who presented in mid to late childhood with progressive varus deformity of their legs due to hypophosphatemic rickets caused by mutations in the ENPP 1 gene.
Hearing loss was not previously thought to be one of the features of the disease entities and was merely regarded as a complication rather than a part of the disease. Loss of function mutations of the ecto-nucleotide pyrophosphatase/pyrophosphodiesterase 1 gene ( ENPP 1) causes a wide spectrum of phenotypes, ranging from lethal generalized arterial calcification of infancy to hypophosphatemic rickets with hypertension. Steichen-Gersdorf, Elisabeth Lorenz-Depiereux, Bettina Strom, Tim Matthias Shaw, Nicholas JĪutosomal recessive hypophosphatemic rickets 2 (ARHR2) is a rare form of renal tubular phosphate wasting disorder. Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP 1.
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