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Deletion Xq27.3q28 in female patient with global developmental delays and skewed X-inactivation.

Marshall LS, Simon J, Wood T, Peng M, Owen R, Feldman GS, Zaragoza MV - BMC Med. Genet. (2013)

Bottom Line: Gene deletions of the Xq27-28 region are less frequently found in either condition with rare reports in females.Contrary to previous reports, our observations do not support a primary role of the Xq27-28 region in X-inactivation.A review of the genes in the deletion region revealed several potential genes that may contribute to the patient's developmental delays, and sequencing of the active X chromosome may provide insight into the etiology of this clinical presentation.

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ABSTRACT

Background: Global developmental delay and mental retardation are associated with X-linked disorders including Hunter syndrome (mucopolysaccharidosis type II) and Fragile X syndrome (FXS). Single nucleotide mutations in the iduronate 2-sulfatase (IDS) gene at Xq28 most commonly cause Hunter syndrome while a CGG expansion in the FMR1 gene at Xq27.3 is associated with Fragile X syndrome. Gene deletions of the Xq27-28 region are less frequently found in either condition with rare reports in females. Additionally, an association between Xq27-28 deletions and skewed X-inactivation of the normal X chromosome observed in previous studies suggested a primary role of the Xq27-28 region in X-inactivation.

Case presentation: We describe the clinical, molecular and biochemical evaluations of a four year-old female patient with global developmental delay and a hemizygous deletion of Xq27.3q28 (144,270,614-154,845,961 bp), a 10.6 Mb region that contains >100 genes including IDS and FMR1. A literature review revealed rare cases with similar deletions that included IDS and FMR1 in females with developmental delay, variable features of Hunter syndrome, and skewed X-inactivation of the normal X chromosome. In contrast, our patient exhibited skewed X-inactivation of the deleted X chromosome and tested negative for Hunter syndrome.

Conclusions: This is a report of a female with a 10.6 Mb Xq27-28 deletion with skewed inactivation of the deleted X chromosome. Contrary to previous reports, our observations do not support a primary role of the Xq27-28 region in X-inactivation. A review of the genes in the deletion region revealed several potential genes that may contribute to the patient's developmental delays, and sequencing of the active X chromosome may provide insight into the etiology of this clinical presentation.

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Facial Features. Front (A), three-quarter (B), and profile (C) views of the patient.
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Figure 1: Facial Features. Front (A), three-quarter (B), and profile (C) views of the patient.

Mentions: At age 23 months old, she was evaluated in the Medical Genetics clinic (MVZ and JS). Physical examination (Figure 1) showed that the patient had wide eye fissures, down turned corners of the lips, full cheeks, temporal narrowing, gaps between her teeth and long eyelashes. Her fingers were tapered with a hypoplastic distal crease of her left index finger, and she wore corrective lenses for myopia. She had limited speech and mild central hypotonia. Detailed pedigree analysis showed that she has healthy parents, two older siblings (a 14-year-old maternal half-brother and a 3-1/2-year-old full sister), and two paternal first cousins with autism and Asperger syndrome. There was no known consanguinity.


Deletion Xq27.3q28 in female patient with global developmental delays and skewed X-inactivation.

Marshall LS, Simon J, Wood T, Peng M, Owen R, Feldman GS, Zaragoza MV - BMC Med. Genet. (2013)

Facial Features. Front (A), three-quarter (B), and profile (C) views of the patient.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643848&req=5

Figure 1: Facial Features. Front (A), three-quarter (B), and profile (C) views of the patient.
Mentions: At age 23 months old, she was evaluated in the Medical Genetics clinic (MVZ and JS). Physical examination (Figure 1) showed that the patient had wide eye fissures, down turned corners of the lips, full cheeks, temporal narrowing, gaps between her teeth and long eyelashes. Her fingers were tapered with a hypoplastic distal crease of her left index finger, and she wore corrective lenses for myopia. She had limited speech and mild central hypotonia. Detailed pedigree analysis showed that she has healthy parents, two older siblings (a 14-year-old maternal half-brother and a 3-1/2-year-old full sister), and two paternal first cousins with autism and Asperger syndrome. There was no known consanguinity.

Bottom Line: Gene deletions of the Xq27-28 region are less frequently found in either condition with rare reports in females.Contrary to previous reports, our observations do not support a primary role of the Xq27-28 region in X-inactivation.A review of the genes in the deletion region revealed several potential genes that may contribute to the patient's developmental delays, and sequencing of the active X chromosome may provide insight into the etiology of this clinical presentation.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Global developmental delay and mental retardation are associated with X-linked disorders including Hunter syndrome (mucopolysaccharidosis type II) and Fragile X syndrome (FXS). Single nucleotide mutations in the iduronate 2-sulfatase (IDS) gene at Xq28 most commonly cause Hunter syndrome while a CGG expansion in the FMR1 gene at Xq27.3 is associated with Fragile X syndrome. Gene deletions of the Xq27-28 region are less frequently found in either condition with rare reports in females. Additionally, an association between Xq27-28 deletions and skewed X-inactivation of the normal X chromosome observed in previous studies suggested a primary role of the Xq27-28 region in X-inactivation.

Case presentation: We describe the clinical, molecular and biochemical evaluations of a four year-old female patient with global developmental delay and a hemizygous deletion of Xq27.3q28 (144,270,614-154,845,961 bp), a 10.6 Mb region that contains >100 genes including IDS and FMR1. A literature review revealed rare cases with similar deletions that included IDS and FMR1 in females with developmental delay, variable features of Hunter syndrome, and skewed X-inactivation of the normal X chromosome. In contrast, our patient exhibited skewed X-inactivation of the deleted X chromosome and tested negative for Hunter syndrome.

Conclusions: This is a report of a female with a 10.6 Mb Xq27-28 deletion with skewed inactivation of the deleted X chromosome. Contrary to previous reports, our observations do not support a primary role of the Xq27-28 region in X-inactivation. A review of the genes in the deletion region revealed several potential genes that may contribute to the patient's developmental delays, and sequencing of the active X chromosome may provide insight into the etiology of this clinical presentation.

Show MeSH
Related in: MedlinePlus