China
Africa
Explore chapters and articles related to this topic
Endocrine and reproductive disorders
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Seckel syndrome (autosomal recessive) is a cause of severe growth failure and microcephaly and is the best recognised of the group of conditions known collectively as ‘microcephalic osteodysplastic primordial dwarfism’. Next-generation sequencing (NGS) gene panels are available to help achieve a diagnosis in this group.
Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Synonyms: MOPD; MOPD1; MOPD I; MOPD3; MOPD III; osteodysplastic primordial dwarfism, type I; brachymelic primordial dwarfism; Taybi-Linder syndrome; TALS; cephaloskeletal dysplasia; low-birth-weight dwarfism with skeletal dysplasia; osteodysplastic primordial dwarfism, type III; MOPD, Caroline Crachami type; MOPD, Sicilian fairy type
Genetics of Endocrine Disorders and Diabetes Mellitus
Published in George H. Gass, Harold M. Kaplan, Handbook of Endocrinology, 2020
Bess Adkins Marshall, Abby Solomon Hollander
A relatively large number of defects have been described in the insulin receptor gene in patients with three rare syndromes: the syndrome of Type A severe insulin resistance, characterized by marked hyperinsulinemia and insulin resistance, acanthosis nigricans, and hyperandrogenism of ovarian origin;39 leprechaunism, characterized by severe primordial dwarfism, hyperinsulinism, and fasting hypoglycemia;40 and Rabson-Mendenhall syndrome, characterized by insulin resistance, abnormal dentition, and thickened nails.41 Some of these mutations are outlined in Table 2. In many cases defects in the binding of insulin,42–46 the kinase activity of the receptor,43,47-55 mRNA abundance,56,57 or the posttranslational processing or trafficking of the receptor43,45,58–60 have been found in these mutant receptors. One mutation appeared to cause constitutive activation of receptor autophosphorylation, kinase activity, and glucose transport.61 Some of the mutations act in a “dominant-negative” fashion, causing severe insulin resistance in the heterozygous state despite the presence of a normal receptor allele.49,51,52,55 One functionally silent mutation,62,63 Val985 to Met, has been found in patients with Type A insulin resistance, NIDDM, and in normal subjects.62–65 It is not clear why defects in the receptor present with varying clinical syndromes. Insulin receptor defects appear thus far to be the cause of all cases of leprechaunism and the Rabson-Mendenhall syndrome, both of which are extremely rare. However, insulin receptor defects may be only a minor cause of the more common Type A severe insulin resistance syndrome. In a study of 22 women with this syndrome, only one had a detectable defect in the insulin receptor.64
Primary Immunodeficiency and Thrombocytopenia
Published in International Reviews of Immunology, 2022
Maryam Mohtashami, Azadehsadat Razavi, Hassan Abolhassani, Asghar Aghamohammadi, Reza Yazdani
Another syndrome is Microcephalic osteo-dysplastic primordial dwarfism type 1 (MOPD1). This deficiency is caused by mutations in the RNU4ATAC gene, which is responsible for encoding the small nuclear RNA (snRNA) U4atac [77].. Although the phenotype of Roifman syndrome and MOPD 1, called Taybi-Linder syndrome, are different from each other, both of them originate from a mutation in the RNU4ATAC gene. On the other side, megakaryopoiesis from peripheral blood-derived CD34+ hematopoietic stem cells (HSCs) in patients with Roifman syndrome are decreased under in vitro conditions, so it is deduced that platelet production reduced. Further supportive evidence has provided that despite the association of platelet with elevated tubulin, actin and alpha and dense granule, aggregation of platelets against agonists such as ATP has not increased. Besides, thrombocytopenia is a striking feature of MOPD1 deficiency [20, 46].
A homozygous POC1B variant causes recessive cone-rod dystrophy
Published in Ophthalmic Genetics, 2021
Ann-Marie C. Peturson, Nicole C. L. Noel, Ian M. MacDonald
POC1A, the paralog of POC1B, also encodes a centriolar protein. POC1A and POC1B proteins localize to the centrosome and contribute to centriole stability (4). There appears to be partially redundant functions of POC1A and POC1B in the centrosome of some cells, as co-knockdown is required to impair centrosome structure in HeLa cells (4). However, knockdown of POC1B alone negatively impacts HeLa cell proliferation (4); this indicates that while POC1A and POC1B may have similar functions within the centrosome, POC1B may play a unique, more integral role than POC1A in specific cell types. Potential divergences in POC1A and POC1B function between tissue or cell types are further highlighted by functional studies and disease manifestation. There is conflicting data surrounding whether POC1A is required for cilia formation (2,15), suggesting that there may be a tissue or cell type-specific influence of POC1A on ciliogenesis. Pathogenic POC1A variants have been reported in a form of primordial dwarfism (15,16), but POC1B has not been associated with short stature conditions – this may be due to a lack of POC1B requirement in cells related to long bone growth, lethality of POC1B variants that would otherwise cause short stature, or inadequate investigation of POC1B in patients with primordial dwarfism. No ocular conditions or retinal dystrophies are associated with POC1A and whether POC1A plays a role in basal body stability within photoreceptor cells is currently unknown.
Novel compound heterozygous mutations of PCNT gene in MOPD type II with central precocious puberty
Published in Gynecological Endocrinology, 2021
Yaping Ma, Zhuangjian Xu, Jinling Zhao, Handan Shen
Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II) is a highly harmful autosomal recessive genetic disease, characterized by intrauterine growth restriction, postnatal growth defects, and microcephaly [1]. It is mainly caused by the functional mutations in PCNT gene. The PCNT gene, mapped to 21q22.3, spans 122 kb of genomic sequence and contains 47 exons. It encodes pericentrin, a critical centrosomal protein. Pericentrin comprises 3,336 amino acid residues [2]. Pericentrin serves as a multifunctional scaffold for anchoring a wide range of centrosomal proteins and protein complexes during cell division [3] and interacts with g-tubulin which is required for microtubule nucleation [4]. The phenotype caused by PCNT mutations might reflect a role for spindle dysfunction in MOPD II. The disruption of pericentrin can lead to mislocalization of proteins, and cause mitotic spindle defects, chromosome missegregation, mitotic failure, cell arrest, and/or cell death [3].