Lipoprotein lipase (LPL) deficiency, caused by mutations in the LPL gene, is a rare autosomal recessive disorder manifesting in early childhood with recurrent abdominal pain, hepatosplenomegaly, acute pancreatitis, lipaemia retinalis and eruptive xanthomas. Typical laboratory findings are lactescent serum, extreme hypertriglyceridaemia and hypercholesterolaemia. The diagnostics is based on postheparin serum LPL assay and DNA analyses of the LPL gene. We report clinical, biochemical and molecular data of three children with LPL deficiency. One child manifested since the first week of life with recurrent abdominal pain (Patient 1), the second with abdominal distension and hepatosplenomegaly since the second month of life (Patient 3) and patient 2, asymptomatic younger brother of patient 1, was diagnosed in the first week of life. Lipaemia retinalis and splenomegaly were present in two symptomatic children, hepatomegaly in patient 3 and acute pancreatitis in patient 1. All children had lactescent serum, profound hypertriglyceridaemia (124 ± 25 mmol/l; controls < 2.2), hypercholesterolaemia (22.8 ± 7.3 mmol/l, controls < 4.2) and their LPL immunoreactive mass in serum did not increase after heparin injection. Molecular analyses revealed that both siblings are homozygous for novel mutation c.476C > G in the LPL gene changing the conserved amino acid of the catalytic centre. The third patient is a compound heterozygote for mutations c.604G>A and c.698A>G in the LPL gene, both affecting highly conserved amino acids. We conclude that LPL deficiency must be considered in neonates and young infants with abdominal pain and hypertriglyceridaemia because early treatment might prevent development of life-threatening acute pancreatitis.
- MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- hyperlipoproteinemie typ I krev diagnóza genetika patofyziologie MeSH
- kojenec MeSH
- lidé MeSH
- lipoproteinlipasa krev genetika MeSH
- mutace * MeSH
- předškolní dítě MeSH
- věk při počátku nemoci MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
98 s. : il., tab., grafy ; 34 cm
The tumor suppressor gene NKX3.1 and the LPL gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of LPL loss may be misinterpreted due to its co-deletion with NKX3.1, a well-established event in prostate carcinogenesis. This study investigates whether LPL deletion represents a biologically relevant event or occurs merely as a bystander to NKX3.1 loss. We analyzed 28 formalin-fixed paraffin-embedded prostate cancer samples with confirmed LPL deletion and 28 without. Immunohistochemical staining was performed, and previously published whole-genome sequencing data from 103 prostate cancer patients were reanalyzed. Deletion of the 8p21.3 region was associated with higher Gleason grade groups. While NKX3.1 expression was significantly reduced in prostate cancer compared to benign prostatic hyperplasia, LPL protein expression showed no significant difference between cancerous and benign tissue, nor was it affected by the 8p21.3 deletion status. Copy number analysis confirmed the co-deletion of NKX3.1 and LPL in 54 patients. Notably, NKX3.1 loss without accompanying LPL deletion was observed in eight additional cases. These findings suggest that LPL deletion is a passenger event secondary to NKX3.1 loss and underscore the importance of cautious interpretation of cytogenetic findings involving the LPL locus.
- MeSH
- delece genu * MeSH
- homeodoménové proteiny * genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty * genetika patologie metabolismus MeSH
- progrese nemoci MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- transkripční faktory * genetika metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
The clinical course of chronic lymphocytic leukemia (CLL) is highly variable. Patients with unmutated IGHV (U-CLL) usually progress rapidly, whereas patients with mutated IGHV (M-CLL) have a more indolent disease. The expression of several genes correlates closely with the IGHV mutational status and could be used to assess prognosis in CLL. We analyzed the prognostic relevance of COBLL1, LPL, and ZAP70 gene expression, which correlated with IGHV mutational status (p < 0.0001), in 117 CLL patients and established a prognostic parameter dividing the tested cohort according to the disease aggressiveness. Our prognostic parameter was validated on an independent cohort of 161 CLL patients and achieved a high accuracy (94%). Patients divided according to the prognostic parameter differ in overall survival and time to first treatment (p < 0.0001, HR = 2.300/5.970, 95% CI: 1.587-3.450/4.621-15.86). Our approach provides a reliable alternative method to prognosis assessment via IGHV mutational status analysis.
- MeSH
- analýza přežití MeSH
- chronická lymfatická leukemie diagnóza genetika mortalita MeSH
- dospělí MeSH
- exprese genu MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipoproteinlipasa genetika MeSH
- mutace * MeSH
- nádorové biomarkery MeSH
- prognóza MeSH
- progrese nemoci MeSH
- protein-tyrosinkináza ZAP-70 genetika MeSH
- reprodukovatelnost výsledků MeSH
- ROC křivka MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- těžké řetězce imunoglobulinů genetika MeSH
- transkripční faktory genetika MeSH
- variabilní oblast imunoglobulinu genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Familiárna chylomikronémia (Familial chylomicronemia syndrome – FCS) je autosómovo recesívne dedičné metabolické ochorenie, ktoré spôsobujú mutácie v génoch, ktoré majú kľúčovú úlohu v lipolýze lipoproteínov bohatých na triglyceridy. Charakteristickým prejavom FCS je prítomnosť chylomikrónov v plazme aj po 12-hodinovom lačnení. Najčastejšou príčinou tohto ochorenia sú mutácie v géne lipoproteinovej lipázy (LPL), ktoré sa zisťujú u viac ako 80 % pacientov. Táto forma FCS sa tiež nazýva deficiencia lipoproteinovej lipázy (LPLD). Populačný výskyt FCS sa udáva 1–2 na 1 milión. Avšak pokrok v diagnostike DNA poukazuje na to, že výskyt môže byť vyšší. Pacientka, ktorej prípad prezentujeme, prekonala 9-krát recidívu akútnej pankreatitdy. Až 2. tehotenstvo skončilo úspešne bez perinatálnych komplikácií a pôrodom zdravého chlapca. Úspech je výsledkom intenzívnej multidisciplinárnej starostlivosti, dôslednému diétnemu plánovaniu a edukácií a správnemu rozhodnutiu začať liečbu plazmaferézou v 3. trimestri gravidity.
Familial chylomicronemia (Familial chylomicronemia syndrome – FCS) is an autosomal recessive inherited metabolic disorder which causes mutations in the genes which have a central role in lipolysis of triglyceride-rich lipoproteíns. A characteristic manifestation of FCS is the presence of chylomicrons in plasma also after 12- hour fasting. The most common cause of this disorder are mutations in the lipoprotein lipase (LPL) gene that are found in more than 80% patients. This form of FCS is also called lipoprotein lipase deficiency (LPLD). Incidence of FCS in the population is reported to be 1–2 per 1 million. Nonetheless the progress in DNA diagnostics suggests that the incidence may be higher. A patient whose case we present has overcome recurrent acute pancreatitis 9 times. It was only her 2nd pregnancy which was free from perinatal complications and ended by birth of a healthy boy. The success is the result of intensive multidisciplinary care, consistent diet planning and education and the right decision to commence the plasmapheresis treatment in the 3rd trimester of pregnancy.
- MeSH
- chylomikrony krev MeSH
- dospělí MeSH
- hyperlipoproteinemie typ I * diagnóza komplikace terapie MeSH
- komplikace těhotenství MeSH
- lidé MeSH
- plazmaferéza MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- charakteristické znaky pohlaví MeSH
- dospělí MeSH
- hyperlipidemie MeSH
- lidé MeSH
- lipasa krev MeSH
- lipolýza imunologie MeSH
- postprandiální období MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
