Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked dominant Conradi-Hunermann-Happle syndrome (CDPX2; MIM 302960) is a rare chondrodysplasia punctata primarily affecting females. CDPX2 is presumed lethal in males, although a few affected males have been reported. CDPX2 is a cholesterol biosynthetic disorder due to 3-beta-hydroxysteroid-delta8,delta7-isomerase deficiency caused by mutations in the emopamil binding protein (EBP) gene. A 2.5-year-old Caucasian male was followed from the age of 6 weeks and noted to have significant developmental delay, hypotonia, seizures, and patchy hypopigmentation. Multiple congenital anomalies included a unilateral cataract, esotropia, crossed renal ectopia, stenotic ear canals, and failure to thrive, requiring G-tube placement. Multiple minor anomalies and ptosis were noted. No skeletal asymmetry or chondrodysplasia punctata were noted on skeletal survey at 6 weeks and 13 months. An extensive genetic work-up including cholesterol (126-176 mg/dl) and 7-dehydrocholesterol was unrevealing. However, the levels of 8(9)-cholestenol and 8-dehydrocholesterol were mildly increased in plasma, which was confirmed in cultured fibroblasts. This prompted molecular analysis of the EBP gene, which revealed a novel hemizygous (nonmosaic) mutation in exon 2 (L18P). Two restriction digests were developed that confirmed this mutation in skin fibroblasts, blood, and buccal cells (all nonmosaic). We determined that the patient's mother (adopted) also has the L18P mutation enabling prenatal diagnosis of a normal male fetus. She has normal stature, no asymmetry, no cataracts at this time, and has a patch of hyperpigmentation on her chest best visualized on Woods lamp examination, characteristic of CDPX2. The mild maternal phenotype has been described previously. However, this nonmosaic missense mutation has resulted in a severe phenotype in her surviving son.
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PMID:Molecular, biochemical, and phenotypic analysis of a hemizygous male with a severe atypical phenotype for X-linked dominant Conradi-Hunermann-Happle syndrome and a mutation in EBP. 1536 6

Our improved tools to identify the aetiologies in patients with multiple abnormalities resulted in the finding that some patients have more than a single genetic condition and that some of the diagnoses made in the past are acquired rather than inherited. However, limited knowledge has been accumulated regarding the phenotypic outcome of the interaction between different genetic conditions identified in the same patients. We report a newborn girl with brachytelephalangic chondrodysplasia punctata (BCDP) as well as frontonasal dysplasia, ptosis, bilateral hearing loss, vertebral anomalies, and pulmonary hypoplasia who was found, by whole exome sequencing, to have a de novo pathogenic variant in RAF1 (c.770C>T, [p.Ser257Leu]) and a likely pathogenic variant in SIX2 (c.760G>A [p.A254T]), as well as maternal systemic lupus erythematosus (SLE). This case shows that BCDP is most probably not a diagnostic entity and can be associated with various conditions associated with CDP including maternal SLE.
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PMID:Maternal SLE and brachytelephalangic chondrodysplasia punctata in a patient with unrelated de novo RAF1 and SIX2 variants. 3250 14