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Case Reports
. 2008 Jul 15;146A(14):1842-7.
doi: 10.1002/ajmg.a.32381.

Donnai-Barrow syndrome (DBS/FOAR) in a child with a homozygous LRP2 mutation due to complete chromosome 2 paternal isodisomy

Sibel Kantarci  1 , Nicola K Ragge, N Simon Thomas, David O Robinson, Kristin M Noonan, Meaghan K Russell, Dian Donnai, F Lucy Raymond, Christopher A Walsh, Patricia K Donahoe, Barbara R Pober
Affiliations
Case Reports

Donnai-Barrow syndrome (DBS/FOAR) in a child with a homozygous LRP2 mutation due to complete chromosome 2 paternal isodisomy

Sibel Kantarci et al. Am J Med Genet A. .

Abstract

Donnai-Barrow syndrome [Faciooculoacousticorenal (FOAR) syndrome; DBS/FOAR] is a rare autosomal recessive disorder resulting from mutations in the LRP2 gene located on chromosome 2q31.1. We report a unique DBS/FOAR patient homozygous for a 4-bp LRP2 deletion secondary to paternal uniparental isodisomy for chromosome 2. The propositus inherited the mutation from his heterozygous carrier father, whereas the mother carried only wild-type LRP2 alleles. This is the first case of DBS/FOAR resulting from uniparental disomy (UPD) and the fourth published case of any paternal UPD 2 ascertained through unmasking of an autosomal recessive disorder. The absence of clinical symptoms above and beyond the classical phenotype in this and the other disorders suggests that paternal chromosome 2 is unlikely to contain imprinted genes notably affecting either growth or development. This report highlights the importance of parental genotyping in order to give accurate genetic counseling for autosomal recessive disorders.

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Figures

Fig. 1
Fig. 1
Proband at 8 years of age with characteristic craniofacial features of DBS/FOAR syndrome. Note hypertelorism, downslanting palpebral fissures, and iris colobomas.
Fig. 2
Fig. 2
The family pedigree and sequencing chromatograms of the LRP2 gene showing a homozygous 4-bp deletion (c.11469_11472delTTTG, exon 60) in the proband (indicated by the small bar), a heterozygous deletion in the father and the sister (indicated by the long dashed bar). The mother does not carry the mutation (indicated by the solid bar); appearance of her chromatogram is comparable to that of a normal control. Wt, wild-type.
Fig. 3
Fig. 3
Idiogram of chromosome 2 showing genotype analyses of family members using 19 short tandem repeat (STR) markers from chromosome 2. Proband was homozygous for all markers as well as the LRP2 mutation (encircled in bold) which originated only from the carrier father. A total of 14 informative markers indicated paternal isodisomy for chromosome 2. The healthy sister showed normal bi-parental inheritance on chromosome 2; note possible recombination between paternal markers D2S2330 and LRP2.
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