Rare Diseases Symptoms Automatic Extraction

DNA-based prenatal diagnosis of harlequin ichthyosis and characterization of ABCA12 mutation consequences.

[harlequin ichthyosis]

Until the identification of ABCA12 as the causative gene, prenatal diagnosis (PD) for harlequin ichthyosis (HI) had been performed by electron microscopic observation of fetal skin biopsy samples. We report the first case of HI DNA-based PD. Direct sequence analysis of ABCA12 revealed that the deceased proband was a compound heterozygote for two novel mutations. The maternal nonsense mutation p.Ser1249Term likely leads to nonsense-mediated messenger RNA decay. The paternal mutation c.7436G>A affects the last codon of exon 50 and was expected to be a splice site mutation. For their third pregnancy, the parents requested PD. Direct sequence analysis of fetal genomic DNA from amniotic fluid cells at 17 weeks gestation revealed the fetus was a compound heterozygote for both mutations. The parents requested the pregnancy to be terminated. Analysis of ABCA12 transcripts of cultured keratinocytes from the abortus showed the presence of six abnormally spliced products from the allele carrying the splice site mutation. Four of them lead to premature termination codons whereas the two others produced shortened proteins missing 21 and 31 amino acids from the second ATP-binding cassette. This report provides evidence for residual ABCA12 expression in HI, and demonstrates the efficiency of early DNA-based PD of HI.

Diseases presenting "first case" symptom

  • achondroplasia
  • adrenal incidentaloma
  • allergic bronchopulmonary aspergillosis
  • alpha-thalassemia
  • aniridia
  • aromatase deficiency
  • canavan disease
  • carcinoma of the gallbladder
  • child syndrome
  • cholangiocarcinoma
  • classical phenylketonuria
  • coats disease
  • cohen syndrome
  • congenital toxoplasmosis
  • cushing syndrome
  • cutaneous mastocytosis
  • dedifferentiated liposarcoma
  • dentin dysplasia
  • dracunculiasis
  • dystrophic epidermolysis bullosa
  • epidermolysis bullosa simplex
  • esophageal adenocarcinoma
  • esophageal carcinoma
  • fabry disease
  • familial mediterranean fever
  • focal myositis
  • gm1 gangliosidosis
  • harlequin ichthyosis
  • hodgkin lymphoma, classical
  • homocystinuria without methylmalonic aciduria
  • junctional epidermolysis bullosa
  • kabuki syndrome
  • krabbe disease
  • lamellar ichthyosis
  • legionellosis
  • liposarcoma
  • locked-in syndrome
  • malignant atrophic papulosis
  • monosomy 21
  • neonatal adrenoleukodystrophy
  • oculocutaneous albinism
  • omenn syndrome
  • papillon-lefèvre syndrome
  • pendred syndrome
  • pleomorphic liposarcoma
  • primary effusion lymphoma
  • primary hyperoxaluria type 1
  • proteus syndrome
  • pyomyositis
  • systemic capillary leak syndrome
  • thoracic outlet syndrome
  • von hippel-lindau disease
  • waldenström macroglobulinemia
  • well-differentiated liposarcoma
  • werner syndrome
  • wolf-hirschhorn syndrome
  • x-linked adrenoleukodystrophy

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