Two cases of confined placental mosaicism for chromosome 4, including one with maternal uniparental disomy

Congenital afibrinogenaemia caused by uniparental isodisomy of chromosome 4 containing a novel 15-kb deletion involving fibrinogen Aα-chain gene

“…Paternity test was accomplished by PCR amplification of 10 short tandem repeat (STR) markers from chromosomes 2, 3,4,8,11,12,16,18,19, and 21 using the AmpFlSTRSMGPluskit (Applied Biosystems), according to the manufacturer's instructions.…”

“…Only five cases of maternal UPD for chromosome 4 have been reported so far. Three were partial UPDs, involving 4q21 -35 in a Japanese man affected by abetalipoproteinaemia, 15 4p13 -16 in a patient affected by Ellis-van Creveld syndrome, 16 and 4p15 -16 in a child with trisomy 21; 17 one was a complete UPD in a normally developed foetus who died in the uterus probably because of the high level of mosaicism for trisomy 4 found in placental trophoblast, 18 and one was a case of isochromosome 4 (46, À4, À4, þ i4q, þ i4p) in a woman with multiple miscarriages. 19 This study describes the first case of congenital afibrinogenaemia caused by uniparental isodisomy (iUPD) of chromosome 4 containing a novel homozygous large deletion (approximately 15 kb).…”

Mosaic trisomy 4: Long-term outcome on the first reported liveborn

“…To our knowledge, a prenatal diagnosis of trisomy 4 mosaicism resulting in a liveborn child has been described in only five cases [Marion et al, 1990;Hsu et al, 1997;Zaslav et al, 2000;Kuchinka et al, 2001;Wieczorek et al, 2003]. Three of the five cases lacked confirmation of the abnormality in samples collected from the child after delivery [Hsu et al, 1997;Zaslav et al, 2000;Kuchinka et al, 2001], and likely represent cases of confined placental mosaicism. In an effort to provide long-term followup clinical information on this rare chromosome abnormality, we have revisited our patient, N.J., the first reported liveborn with mosaic trisomy 4.…”

“…In a previous report, we described the first liveborn with trisomy 4 mosaicism [Marion et al (1990) Am J Med Genet 37:362-365]. To our knowledge, since our original report, there have been only four additional reports of a prenatal diagnosis of mosaic trisomy 4 resulting in a liveborn child [Hsu et al (1997) Prenat Diag 17:201-242; Kuchinka et al (2001) Prenat Diag 21:36-39; Wieczorek et al (2003) Prenat Diag 23:128-133; Zaslav et al (2000) Am J Med Genet 95:381-384]. Three of the more recent reports lacked confirmation of the mosaicism in tissue samples collected from the child after delivery, and likely represent cases of confined placental mosaicism.…”

Implications of fetoplacental mosaicism on cell‐free DNA testing: a review of a common biological phenomenon

“…In the second situation (CPM Types 1 and 3), the only rare mosaic trisomies in CV showing a likelihood of fetal confirmation are the mosaic trisomies 4 (T4) and 16 (T16). Clinical consequences of a fetal mosaic T16 or T4 are unpredictable and largely dependent on the mosaicism level in the fetus. As for ‘large’ partial CNVs, and even for rare full chromosomal trisomies, their presence in fetal tissue in a consistent level of mosaicism would trigger fetal ultrasound abnormalities or a lethal phenotype.…”