Segmental and full paternal isodisomy for chromosome 14 in three patients: Narrowing the critical region and implication for the clinical features

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Abstract
We report on segmental and full paternal isodisomy for chromosome 14 in three previously unreported Japanese patients. Patient 1 was a ‐year‐old girl, Patient 2 was a male neonate, and Patient 3 was a ‐year‐old girl. Physical examination at birth showed various somatic features characteristic of paternal uniparental disomy for chromosome 14 (upd(14)pat) such as hairy forehead, protruding philtrum, micrognathia, small thorax, and abdominal wall defects in Patients 1–3, and the constellation of somatic features was persistently observed in Patients 1 and 3. Radiological studies at birth delineated unique bell‐shaped thorax with coat‐hanger appearance of the ribs in Patients 1–3, but the thoracic deformity ameliorated in Patients 1 and 3 by mid childhood. Chromosome analysis showed a 46,XX karyotype in Patients 1 and 3 and was not performed in Patient 2. Microsatellite analysis indicated full paternal isodisomy for chromosome 14 in Patients 1 and 2 and segmental paternal isodisomy for chromosome 14 distal to D14S981 at 14q23.3 in Patient 3. Methylation specific PCR assay for the differentially methylated region (DMR) of GTL2 at 14q32 yielded positive products with methylated allele specific primers and no products with unmethylated allele specific primers in Patients 1–3. Since clinical phenotype was similar between Patient 3 with segmental upd(14)pat and Patients 1 and 2 with full upd(14)pat, the results are keeping with the 14q32 localized imprinted genes as the critical components of the phenotype observed in upd(14)pat and help narrow the search for additional genes to the ∼40 Mb region distal to D14S981. Furthermore, it is likely that the characteristic thoracic deformity ameliorates with age.