Maternal Uniparental Disomy for Chromosome 14

Abstract

A girl carrying a de novo balanced 13-14 robertsonian translocation showed a clinical phenotype with severe hypotonia, hyperextensible joints, frontal bossing, asymmetric face, no mental retardation, severe scoliosis and motor delay. In situ hybridization analysis on chromosome spreads revealed the presence of the two centromeres in the rearranged chromosomes. Molecular analysis on genomic DNA showed the presence in the proposita of two chromosomes 14 of maternal origin and no chromosome 14 from the father indicating a maternal monocentric uniparental disomy for chromosome 14 (mUPD14). Our patient shows several similarities with other reported cases of mUPD14, suggesting imprinting of a region(s) of chromosome 14 and defining a possible mUPD14 Syndrome.

Maternal uniparental isodisomy for chromosome 14 detected prenatally

“…UPD for chromosome 14 has been reported in 15 cases, the majority involving Robertsonian translocations: 11 cases were upd(14)mat (Temple et al, 1991;Pentao et al, 1992;Antonarakis et al, 1993;Healey et al, 1994;Morichon-Delvallez et al, 1994; Sirchia et al, 1994;Tomkins et al, 1994;Coviello et al, 1995;Papenhausen et al, 1995;Splitt and Goodship, 1997;Miyoshi et al, 1998) and four cases were upd(14)pat (Wang et al, 1991;Papenhausen et al, 1995;Walter et al, 1996;Cotter et al, 1997). Healey et al (1994) reviewed cases of upd(14)mat and common findings included short stature, small hands possibly with hyperextensible joints, hydrocephalus that arrests spontaneously, minor facial anomalies (including high palate), mild to moderate developmental delay (particularly motor delay) and premature puberty.…”

Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q

“…In humans, some imprinting anomalies have been reported in both maternal and paternal disomies for chromosome 14q (mUPD14 and pUPD14, respectively) (Ledbetter & Engel 1995;Engel 1997). Patients with pUPD14 show a musculoskeletal problem and mental retardation (Cotter et al 1997;Wang et al 1991;Papenhausen et al 1995;Walter et al 1996), whereas mUPD leads to short stature and precocious puberty (Antonarakis et al 1993;Temple et al 1991;Pentao et al 1992;Healey et al 1994;Sirchia et al 1994;Coviello et al 1996;Robinson & Langlois 1996;Tomkins et al 1996;Splitt & Goodship 1997;Miyoshi et al 1998b;Berends et al 1999;Fokstuen et al 1999;Martin et al 1999;Ralph et al 1999), suggesting that there are some imprinted genes in this region. We have found that the human homologue, MEG3, is an imprinted gene which is preferentially expressed from the maternal allele.…”

Risk of Mosaicism and Uniparental Disomy Associated with the Prenatal Diagnosis of a Non-Homologous Robertsonian Translocation Carrier

“…A total of 400 cases have been reported to date [15,[17][18][19][20][21][22] (table 2). UPD testing was performed for 1 or 2 of the chromosomes involved in the translocation depending on the chromosome involved and/or the authors, resulting in 687 UPD tests.…”