title: Foetal presentation of cartilage hair hypoplasia with extensive granulomatous inflammation.
abstract: Cartilage-hair-hypoplasia is a rare autosomal recessive metaphyseal dysplasia due to RMRP (the RNA component of the RNase MRP ribonuclease mitochondrial RNA processing complex) gene mutations. So far, about 100 mutations have been reported in the promoter and the transcribed regions. Clinical characteristics include short-limbed short stature, sparse hair and defective cell-mediated immunity. We report herein the antenatal presentation of a female foetus, in whom CHH was suspected from 23 weeks' gestation, leading to a medical termination of the pregnancy at 34 weeks gestation, and thereafter confirmed by morphological and molecular studies. Post-mortem examination confirmed short stature and limbs, and revealed thymic hypoplasia associated with severe CD4 T-cell immunodeficiency along with extensive non caseating epithelioid granulomas in almost all organs, which to our knowledge has been described only in five cases. Molecular studies evidenced on one allele the most frequently reported founder mutation NR_003051: g.70A>G, which is present in 92% of Finnish patients with Cartilage Hair Hypoplasia. On the second allele, a novel mutation consisting of a 10 nucleotide insertion at position -18 of the promoter region of the RMRP gene (M29916.1:g.726_727insCTCACTACTC) was detected. The founder mutation was inherited from the father, and the novel mutation from the mother. To our knowledge, this case report represents the first detailed foetal analysis described in the literature.
authors: Pathology Laboratory, Rouen University Hospital, France.
authors: Marie
authors: M
authors: Crahes
authors: Pascale
authors: P
authors: Saugier-Veber
authors: Sophie
authors: S
authors: Patrier
authors: Moutaz
authors: M
authors: Aziz
authors: Nathalie
authors: N
authors: Pirot
authors: Marie
authors: M
authors: Brasseur-Daudruy
authors: Valérie
authors: V
authors: Layet
authors: Thierry
authors: T
authors: Frébourg
authors: Annie
authors: A
authors: Laquerrière
mesh_terms: D037881:Aborted Fetus / Q000473:pathology*; D005260:Female; D006099:Granuloma / Q000175:diagnosis; D006197:Hair / Q000002:abnormalities* / Q000196:embryology; D006627:Hirschsprung Disease / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics; D007249:Inflammation / Q000175:diagnosis; D007960:Leukocyte Disorders / Q000175:diagnosis; D009154:Mutation; D010009:Osteochondrodysplasias / Q000151:congenital* / Q000175:diagnosis / Q000196:embryology / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis; D000081207:Primary Immunodeficiency Diseases; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: C544035:RMRP non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: Cartilage-hair hypoplasia; Granulomatous inflammation; RMRP mutations; T-cell immunodeficiency