American journal of medical genetics. Part A
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Am. J. Med. Genet. A · Nov 2012
Case ReportsSleep-disordered breathing in Beckwith-Wiedemann syndrome: three patients.
Beckwith-Wiedemann syndrome is associated with craniofacial abnormalities that may predispose patients to sleep-related breathing disorders. There is limited literature on the polysomnography findings for children with this syndrome. Three patients with Beckwith-Wiedemann syndrome underwent polysomnography in our sleep lab and were found to have a variety of sleep-disordered breathing that ranged from obstructive apnea to isolated REM sleep-related hypoxemia-hypoventilation without obstructive apnea. Suspicion for sleep-disordered breathing should be high in children with Beckwith-Wiedemann syndrome.
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Am. J. Med. Genet. A · Nov 2012
Case ReportsAn inherited LMNA gene mutation in atypical Progeria syndrome.
Hutchinson-Gilford Progeria syndrome (HGPS) is a rare genetic disorder, characterized by several clinical features that begin in early childhood, recalling an accelerated aging process. The diagnosis of HGPS is based on the recognition of common clinical features and detection of the recurrent heterozygous c.1824C>T (p. Gly608Gly) mutation within exon 11 in the Lamin A/C encoding gene (LMNA). ⋯ The molecular studies showed the heterozygous mutation c.412G>A (p. Glu138Lys) of the LMNA gene. This mutation, previously reported as a de novo mutation, was inherited from the apparently healthy father who showed a somatic cell mosaicism.
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Am. J. Med. Genet. A · Oct 2012
Phenotypic variability of atypical 22q11.2 deletions not including TBX1.
Interstitial deletions of the chromosome 22q11.2 region are the most common microdeletions in humans. The TBX1 gene is considered to be the major candidate gene for the main features in 22q11.2 deletion syndrome, including congenital heart malformations, (para)thyroid hypoplasia, and craniofacial abnormalities. We report on eight patients with atypical deletions of chromosome 22q11.2. ⋯ Ten similar patients with overlapping distal 22q11.2 deletions have been reported previously. The clinical features of these patients are described and compared to those found in the classic 22q11.2 deletion syndrome. We discuss the possible roles of a position effect or haploinsufficiency of distally located genes (e.g., CRKL) in the molecular pathogenesis of the 22q11.2 deletion syndrome.
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Am. J. Med. Genet. A · Sep 2012
Case ReportsGermline mosaicism of PHOX2B mutation accounts for familial recurrence of congenital central hypoventilation syndrome (CCHS).
Congenital central hypoventilation syndrome (CCHS), a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation, is caused by mutations in the PHOX2B gene. Most mutations occur de novo, but recent evidence suggests that up to 25% are inherited from asymptomatic parents with somatic mosaicism for these mutations. However, to date, germline mosaicism has not been reported. ⋯ The PHOX2B 20/27 expansion was not observed in a paternal sperm sample. This case represents the first reported family with recurrence of PHOX2B mutation-confirmed CCHS without detection of a parental carrier state or mosaicism, confirming the previously hypothesized possibility of germline mosaicism for PHOX2B mutations. This is an important finding for genetic counseling of CCHS families, suggesting that even if somatic mosaicism is not detected in parental samples, there is still reason for careful genetic counseling and consideration of prenatal testing during subsequent pregnancies.