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Unique mosaicism in Prader-Labhart-Willi syndrome--a contiguous gene or aneuploidy syndrome?
B G Kousseff1, T Diamond, Y Essig
1Division of Medical Genetics, University of South Florida, Tampa 33612-4799.
Insights
This study details a Prader-Willi syndrome case with unique chromosomal mosaicism, including partial trisomy and pentasomy of chromosome 15. Findings suggest Prader-Willi syndrome may be a contiguous gene syndrome, not solely aneuploidy.
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- Prader-Willi syndrome (PWS) is a complex genetic disorder.
- Characterized by hypotonia, hyperphagia, obesity, and developmental delays.
- Cytogenetic underpinnings of PWS are diverse, often involving chromosome 15.
Observation:
- A 16-year-old male with PWS presented with infantile hypotonia, feeding issues, and later developed obesity, diabetes, and hypogonadism.
- Cytogenetic analysis revealed complex chromosomal mosaicism: 45,X, t(Y;15) with 15pter-15q12 deletion; 46,X, t(Y;15), dic(15); and 47,X, t(Y;15), dic(15), dic(15).
- The dic(15) represented inverted duplication (inv dup(15)), leading to partial trisomy and pentasomy for the 15pter-15q12 region.
Findings:
- The patient exhibited mosaicism with varying cell line ratios in lymphocytes and fibroblasts.
- The observed chromosomal aberrations, including partial trisomy and pentasomy of chromosome 15, are unique.
- These findings challenge the traditional view of PWS as solely an aneuploidy syndrome.
Implications:
- The complex chromosomal mosaicism in this PWS case suggests a broader spectrum of genetic mechanisms.
- Aberrations in chromosome 15, as seen here, support the hypothesis of PWS as a contiguous gene syndrome.
- Further research into diverse chromosomal abnormalities is crucial for understanding PWS pathogenesis and developing targeted therapies.
Abstract:
A 16-year-old boy with Prader-Labhart-Willi syndrome (PLWS) had hypotonia, feeding difficulties, failure to thrive, strabismus and bilateral inguinal hernias with cryptorchidism during infancy followed by hyperphagia, marked early-onset obesity with insulin-dependent diabetes mellitus and necrobiosis lipoidica diabeticorum, short stature, hypogonadotropic hypogonadism and some of the facial characteristics of the individuals with the PLWS. IQ is estimated around 90. Cytogenetic studies showed mosaicism: 45,X, t(Y;15) with partial deletion 15 (15pter----15q12); 46,X, t(Y;15), dic (15)(15pter----15q12::15q12----15pter) and 47, X, t(Y;15), dic(15), dic(15). The dic(15) was bisatellited, NOR-positive on both arms and represented inv dup(15). Thus, the 2 lines with the dic(15) showed partial trisomy 15 (15pter----15q12) and partial pentasomy 15 (15pter----15q12), respectively. The cell line ratios were different in lymphocyte and fibroblast cultures. The unique cytogenetic findings in this patient, the reports of a variety of chromosome 15 aberrations in PLWS, as well as aberrations of other chromosomes, suggest that the condition is a contiguous gene syndrome rather than an aneuploidy syndrome.