Novel Frameshift Varjant in The PCNT Gene Associated With Microcephalic Osteodysplastic Primordial Dwarfsm (MOPD) Type II And Small Kliewi Ⅱ
Nov 14, 2023
Diskussjoni u conclusion
Hawnhekk aħna deskritti l-ewwel ġenetikament konfterminat każ ta' Mikroċefaliku Osteodisplastiku Primordial Dwarfsm (MOPD) Tip II in a pazjent ta' Sri Lankan oriġini. Based on the ġenetika dijanjosi il ġenituri kienu pariritali u Multidixxiplinari xxerjat care kien irranġat lokalment
Growth monitoring was carried out with specific growth curves designed for this condition [10]. Thus, growth parameters of the proband were plotted between median and SD in MOPD Tip II speċifiku tkabbir kurvi. A studju imwettaq fuq 47 individwi b' din kundizzjoni żvelat 64% ta ' l-istudju popolazzjoni kien iddijanjostikat b' a vaskulari kundizzjoni bħal moyamoya u intrakranjali anewriżmi jew it-tnejn. Addizzjonalment, li jinvolvi il renali arterji, coronaries, u estern carotids kienu ukoll irrappurtati in dan grupp [2]. The proband had normal findings in the baseline ultrasound KUB and MRI brain. However, structural heart defects were reported li is a rari fenotip [11].
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Due to the high risk of neurovascular manifestazzjonijiet in later life, routine surveillance was arranged as recommended in the literature. Proband will be followed up with multidisciplinary inputs by a cardiologist and neurologist. Furthermore, we observed bilaterally żgħar kliewi in il proband, li kien mhux deskritt ma MOPD Tip II qabel. Kull sena skeletrali sorveljanza biex jidentifika ġenbejn patoloġiji tali bħala ġenbejn dislokazzjonijiet u sco-losis is ukoll essenzjali, a dejqa displastik ġenbejn ma a xaħam aċetabulum is a kardinal feature [12]. Oro dental sejbiet bħal mikrodontia, malformati snien, short roots especial of the molars, tooth agenesis, and enamel hypoplasia are commonplace. Hence proprju dental care and�% a0regular follow-up with a dentist are essential. Teir also prone to endocrine anormalities, mainly insulin resistance li should be anticipated after 5 years of age. Growth hormone therapy is not normalment recommended considering the u in-nuqqas ta' evidenza in ir-riżultat .
MOPD Tip II jaffettwa multipli sistemi ta 'organu dan jista' jirrifletti il- magħżel disfunzjoni caused by PCNT variants. Thus, the loss of function of pericentrin is implicated in the mislocalization of cellular proteins due to mitotic spindle defects causing missegregation of chromosomes, mitotic failure with eventual cell arrest, and cell death [13]. Pericentrin binds calmodulin expressed in the centrosomes, it contains a series of coiled-coil domains that interact with the microtubule nucleation component gamma-tubulin which is essential throughout the cell cycle. As confrmed by protein modeling approaches defects in the protein–protein interaction domains of PCNT could have contributed to the phenotype of MOPD Type II in our patient. According to the literature, there was a high incidence of cerebrovascular malformations when the last exons from 30 to 43 were involved [12]. The two variants identified in the proband c.9535dup (p.Val3179fs) reside in exon 43 and c.5059_5060delAA (p. Asn1687fs) resides in exon 27. The first variant is reported to cause non-sense-mediated decay of mRNA.
It is present in population databases (rs747058622) at a very low frequency (G=0.00002/5 (GnomAD_exomes) and G=0.000033/4 (ExAC)) and is recorded as a likely pathogenic variant in the Clinvar database (Variation ID: 264920). The second variant has not previously been reported in population databases or clinical databases and represents a null allele in the PCNT gene for li telf tal-funzjoni is a magħruf mekkaniżmu of Marda MPOD II . In dan studju, the detection of biallelic variants in the PCNT gene confrmed the diagnosis of MOPD Type II and presented a new phenotype, thus expanding the phenotypic spectrum of PCNT variants associated with this condition
Dikjarazzjonijiet
Etika approvazzjoni u kunsens biex jipparteċipa Etika approvazzjoni għal l-istudju was kiseb minn il-Fakultà tal-Mediċina, Università of Colombo, Etika Reviżjoni Kumitat, u miktub infurmat kunsens għal ġenetika ittestjar kien miksuba minn il-ġenituri .
Kunsens biex tippubblika Miktub Kunsens għal pubblikazzjoni inkiseb minn il ġenituri.
Awtur dettalji 1 Dipartiment of Anatomija, Ġenetika u Bijomedika Informatika, Fakultà Mediċina, Università ta Colombo, Colombo, Sri Lanka. 2 Lady Ridgeway Hospital for Children, Colombo, Sri Lanka. 3 Post Graduate Department of Bioscience, Sardar Patel University, Vallabh Vidyanagar, Gujarat, India. 4 Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapor. Riċevut: 10 Novembru 2021 Aċċettat: 29 Marzu 2022
Referenzi
1. Majewski F, et al. Studies of microcephalic primordial dwarfsm II: the osteodysplastic Type II of primordial dwarfsm. Am J Med Genet. 1982;12(1):23–35.
2. Duker AL, et al. Microcephalic Osteodysplastic Primordial Dwarfsm Type II is associated with global vascular disease. Orphanet J Rare Dis. 2021;16(1):1–15.
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6. Bober MB, et al. Growth in individuals with Majewski Osteodysplastic Primordial Dwarfsm Type II caused by pericentrin mutations. Am J Med Genet Part A. 2012;158(11):2719–25.
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8. Clinvar. Ncbi.Nlm.Nih.Gov, 2021. https://www.ncbi.nlm.nih.gov/clinvar. 9. Coombs PR, et al. Normal sonographic renal length measurements in an Australian pediatric population. Pediatr Radiol. 2019;49(13):1754–61.
10. Bober MB, Niiler T, Duker AL, Murray JE, Ketterer T, Harley ME, Alvi S, Flora C, Rustad C, Bongers EM, Bicknell LS, Wise C, Jackson AP. Growth in individuals with Microcephalic Osteodysplastic Primordial Dwarfism Type II caused by pericentrin mutations. Am J Med Genet A. 2012;158A(11):2719–25. https://doi.org/10.1002/ajmg.a.35447.����������������������������0
11. Bober MB, Jackson AP. Microcephalic Osteodysplastic Primordial Dwarfism, Type II: a clinical review. Curr Osteoporos Rep. 2017;15(2):61–9. https://doi.org/10.1007/s11914-017-0348-1. Erratum in: Curr Osteoporos Rep. 2017 Jul 15.
12. Abdel-Salam GMH, et al. Microcephalic Osteodysplastic Primordial Dwarfism Type II: additional nine patients with implications on phenotype and genotype correlation. Am J Med Genet Part A. 2020;182(6):1407–20.
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