Homozygous LMNA p.R582H pathogenic variant reveals increasing effect on the severity of fat loss in lipodystrophy
| Autor: | Suleyman Cem Adiyaman, Hüseyin Onay, Baris Akinci, Elif A. Oral, Ilgin Yildirim Simsir, Utku Erdem Soyaltin, Kristen N. Lee, Canan Altay |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty LMNA Case Report 030209 endocrinology & metabolism Biology Partial lipodystrophy lcsh:Diseases of the endocrine glands. Clinical endocrinology 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Homozygous lcsh:RC648-665 integumentary system Genetic heterogeneity Leptin Congenital Generalized Lipodystrophy Type 1 Generalized lipodystrophy Partial Lipodystrophy Heterozygote advantage General Medicine medicine.disease 030104 developmental biology Endocrinology Lamin A Lipodystrophy |
| Zdroj: | Clinical Diabetes and Endocrinology Clinical Diabetes and Endocrinology, Vol 6, Iss 1, Pp 1-6 (2020) |
| ISSN: | 2055-8260 |
| Popis: | Background Classical heterozygous pathogenic variants of the lamin A/C (LMNA) gene cause autosomal dominant familial partial lipodystrophy type 2 (FPLD2). However, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants, and a few patients have been associated with generalized fat loss. Case presentation Here, we report a patient with a lamin A specific pathogenic variant in exon 11, denoted LMNA (c.1745G > A; p.R582H), present in the homozygous state. Fat distribution was compared radiographically to an unrelated heterozygote LMNA p.R582H patient from another pedigree, a healthy female control, a series of adult female subjects with congenital generalized lipodystrophy type 1 (CGL1, n = 9), and typical FPLD2 (n = 8). The whole-body MRI of the index case confirmed near-total loss of subcutaneous adipose tissue with well-preserved fat in the retroorbital area, palms and soles, mons pubis, and external genital region. This pattern resembled the fat loss pattern observed in CGL1 with only one difference: strikingly more fat was observed around mons pubis and the genital region. Also, the p.R582H LMNA variant in homozygous fashion was associated with lower leptin level and earlier onset of metabolic abnormalities compared to heterozygous p.R582H variant and typical FPLD2 cases. On the other hand, the heterozygous LMNA p.R582H variant was associated with partial fat loss which was similar to typical FPLD2 but less severe than the patients with the hot-spot variants at position 482. Conclusions Our observations and radiological comparisons demonstrate an additive effect of LMNA pathogenic variants on the severity of fat loss and add to the body of evidence that there may be complex genotype-phenotype relationships in this interesting disease known as FPLD2. Although the pathological basis for fat loss is not well understood in patients harboring pathogenic variants in the LMNA gene, our observation suggests that genetic factors modulate the extent of fat loss in LMNA associated lipodystrophy. |
| Databáze: | OpenAIRE |
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