title: A novel frameshift mutation and infrequent clinical findings in two cases with Dyggve-Melchior-Clausen syndrome.
abstract: Dyggve-Melchior-Clausen syndrome (DMC) (MIM #223800) is a rare autosomal-recessive type of skeletal dysplasia accompanied by variable degrees of intellectual disability (ID). It is characterized by progressive spondyloepimetaphyseal dysplasia leading to disproportionate short stature, microcephaly, and coarse facies. The radiographic appearance of generalized platyspondyly with double-humped end plates and the lace-like appearance of iliac crests are pathognomonic in this syndrome. The disorder results from mutations in the dymeclin (DYM) mapped to the 18q12-12.1 chromosomal region. Here, we report two cases with DMC: one with disproportionate short stature, developmental delay, and severe ID with a novel frameshift mutation (c.1028_1056del29) leading to a premature stop codon, and the second patient with classical clinical and radiological features of DMC with mild ID and rectal prolapse, which is very rare. The clinical diagnosis was confirmed with molecular analysis of DYM with a known mutation at c.580C>T (p.R194X). The parents and sibling of the second patient were heterozygous carriers with mild skeletal changes and short stature.
authors.affiliation: Department of Medical Genetics, Cerrahpasa Medical School, Istanbul University Department of Medical Genetics, Zeynep Kamil Women and Children Diseases Education and Research Hospital, Istanbul, Turkey Centre for Human Genetics (Zentrum für Humangenetik, ZHMA), Mannheim, Germany.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Seven
authors.forename: Erkan
authors.initials: E
authors.lastname: Koparir
authors.forename: Alper
authors.initials: A
authors.lastname: Gezdirici
authors.forename: Hatip
authors.initials: H
authors.lastname: Aydin
authors.forename: Heyko
authors.initials: H
authors.lastname: Skladny
authors.forename: Elif
authors.initials: E
authors.lastname: Fenercioğlu
authors.forename: Gülgün
authors.initials: G
authors.lastname: Güven
authors.forename: Ömer Faruk
authors.initials: ÖF
authors.lastname: Karataş
authors.forename: Asuman
authors.initials: A
authors.lastname: Koparir
authors.forename: Mustafa
authors.initials: M
authors.lastname: Özen
authors.forename: Hakan
authors.initials: H
authors.lastname: Ulucan
mesh_terms: D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology; D004392:Dwarfism / Q000235:genetics* / Q000473:pathology; D005260:Female; D016368:Frameshift Mutation; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D008831:Microcephaly / Q000150:complications / Q000235:genetics / Q000473:pathology; D010009:Osteochondrodysplasias / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D011506:Proteins / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C477370:DYM protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins