Maternal uniparental disomy 14 as a cause of intrauterine growth retardation and early onset of puberty,☆☆,

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Abstract

Uniparental disomy for particular chromosomes is increasingly recognized as a cause of abnormal phenotypes in humans either as a result of imprinted genes or, in the case of isodisomy, homozygosity of mutated recessive alleles. We report on the occurrence of maternal uniparental disomy for chromosome 14 (matUPD 14) in a 25-year-old woman with a normal karyotype, normal intelligence but low birth weight, short stature, small hands, and early onset of puberty. Comparison of her phenotype with those of 15 previously described liveborn patients with matUPD14 gives further evidence for an imprinted gene region on chromosome 14 and highlights the necessity to consider this cause in children with intrauterine growth retardation and early onset of puberty caused by acceleration of skeletal maturation. (J Pediatr 1999;134:689-95)

Section snippets

Patient Report

The proposita, a 25-year-old woman, was referred for genetic counseling because of short stature and early onset of puberty. She is the sixth child of healthy unrelated Swiss parents. The mother was 37 and the father 43 years old at delivery. Pregnancy was complicated by oligohydramnios. She was born at term with a birth weight of 1960 g (<10th percentile), length of 47 cm (<10th percentile), and head circumference of 31.5 cm (<10th percentile). Because of poor sucking, she needed nasogastric

RESULTS

Chromosome analysis revealed a normal female karyotype. Molecular studies showed that the proband inherited 2 chromosomes 14 from her mother and none from her father, a result consistent with maternal UPD14. Seven markers revealed maternal heterodisomy, whereas reduction to homozygosity was shown on 3 markers. These results suggest several recombination events on the maternal chromosomes 14 during meiosis I (Table I). Fig 1 gives representative examples for markers showing maternal heterodisomy

DISCUSSION

Tables II and III summarize the cytogenetic and clinical findings of the 16 (including our proband) reported liveborn patients with proven matUPD14.Cases published as abstracts11, 16, 17, 18, 19, 22 often lack detailed clinical information. The interpretation of matUPD14 in 1 report14 must be questioned. The father was not available for analysis, and matUPD14 was suggested on only 2 markers. The absence of a paternal control and homozygosity for only 2 markers do not allow the diagnosis of

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    Supported by Swiss National Foundation Grant 32-42088.94.

    ☆☆

    Reprint requests: Albert Schinzel, MD, Institut für Medizinische Genetik, Rämistrasse 74, 8001 Zürich, Switzerland.

    0022-3476/99/$8.00 + 0  9/21/97903

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