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Clinical and molecular diagnosis of a cartilage-hair hypoplasia with IGF-1 deficiency.

ABSTRACT: Cartilage-hair hypoplasia syndrome (CHH) is a rare autosomal recessive condition characterized by metaphyseal chondrodysplasia and characteristic hair, together with a myriad of other symptoms, being most common immunodeficiency and gastrointestinal complications. A 15-year-old Mexican male initially diagnosed with Hirschsprung disease and posterior immunodeficiency, presents to our department for genetic and complementary evaluation for suspected CHH. Physical, biochemical, and genetic studies confirmed CHH together with IGF-1 deficiency. For this reason, we propose IGF-1 replacement therapy for its well-known actions on hematopoiesis, immune function and maturation, and metabolism. © 2016 Wiley Periodicals, Inc.

SUBMITTER: Castilla-Cortazar I

PROVIDER: S-EPMC6586044 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Clinical and molecular diagnosis of a cartilage-hair hypoplasia with IGF-1 deficiency.

Castilla-Cortázar Inma I Rodríguez De Ita Julieta J Martín-Estal Irene I Castorena Fabiola F Aguirre Gabriel A GA García de la Garza Rocío R Elizondo Martha I MI

American journal of medical genetics. Part A 20161114 2

Cartilage-hair hypoplasia syndrome (CHH) is a rare autosomal recessive condition characterized by metaphyseal chondrodysplasia and characteristic hair, together with a myriad of other symptoms, being most common immunodeficiency and gastrointestinal complications. A 15-year-old Mexican male initially diagnosed with Hirschsprung disease and posterior immunodeficiency, presents to our department for genetic and complementary evaluation for suspected CHH. Physical, biochemical, and genetic studies ...[more]

PMID: 27862957

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Cartilage Hair Hypoplasia: First report from Iran.

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Project description: Not available

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The Safety and Efficacy of Live Viral Vaccines in Patients With Cartilage-Hair Hypoplasia.

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Gynecologic assessment of 19 adult females with cartilage-hair hypoplasia - high rate of HPV positivity.

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Small RNAs derived from lncRNA RNase MRP have gene-silencing activity relevant to human cartilage-hair hypoplasia.

Project description:Post-transcriptional processing of some long non-coding RNAs (lncRNAs) reveals that they are a source of miRNAs. We show that the 268-nt non-coding RNA component of mitochondrial RNA processing endoribonuclease, (RNase MRP), is the source of at least two short (?20 nt) RNAs designated RMRP-S1 and RMRP-S2, which function as miRNAs. Point mutations in RNase MRP cause human cartilage-hair hypoplasia (CHH), and several disease-causing mutations map to RMRP-S1 and -S2. SHAPE chemical probing identified two alternative secondary structures altered by disease mutations. RMRP-S1 and -S2 are significantly reduced in two fibroblast cell lines and a B-cell line derived from CHH patients. Tests of gene regulatory activity of RMRP-S1 and -S2 identified over 900 genes that were significantly regulated, of which over 75% were down-regulated, and 90% contained target sites with seed complements of RMRP-S1 and -S2 predominantly in their 3' UTRs. Pathway analysis identified regulated genes that function in skeletal development, hair development and hematopoietic cell differentiation including PTCH2 and SOX4 among others, linked to major CHH phenotypes. Also, genes associated with alternative RNA splicing, cell proliferation and differentiation were highly targeted. Therefore, alterations RMRP-S1 and -S2, caused by point mutations in RMRP, are strongly implicated in the molecular mechanism of CHH.

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