title: 12q21 Microdeletion in a fetus with Meckel syndrome involving CEP290/MKS4.
abstract: We report on a fetus with Meckel syndrome diagnosed during the 21st gestational week, hydrocephalus and bilateral hyperechogenic kidneys were then detected on ultrasonography. Fetal pathological examination showed facial dysmorphism, occipital meningoencephalocele, characteristic renal cysts, mild hepatic ductal dysplasia, hydrocephalus in association with extreme cerebellar vermis hypoplasia and brainstem anomalies. Molecular and cytogenetic analysis identified a paternally inherited CEP290/MKS4 (MIM611134) (12q21) nonsense mutation and a maternal 12q21 microdeletion. Two cases with such a mechanism have previously been described in the literature, one of them involves an inherited microdeletion. The observation of such cases highlights the existence of a pathogenic mechanism which involves deletion and point mutation, and illustrates how homozygosity can hide hemizygosity when usual sequencing methods are used. The identification of hemizygosity enables to determine precisely the molecular mechanism and to understand some phenotypic variations. As they act as complete loss of function allele, deletions might give indication on the severity of the associated point mutation. This clinical report highlights the importance of fetal pathology following termination of pregnancies in order to guide molecular analysis and the potential role of cytogenetic cryptic disorders in autosomal recessive disease. The use of polymorphic marker analysis in association with FISH or arrayCGH provided an accurate identification of molecular mechanisms, accurate genetic counseling and optimized strategy for next pregnancies or preimplantation diagnosis.
authors: Service de Génétique, laboratoire de Cytogénétique, CHU de Caen, Université Caen Basse-Normandie, France. Electronic address: molin-a@chu-caen.fr.
authors: Arnaud
authors: A
authors: Molin
authors: Guillaume
authors: G
authors: Benoist
authors: Corinne
authors: C
authors: Jeanne-Pasquier
authors: Nadia
authors: N
authors: Elkartoufi
authors: Julie
authors: J
authors: Litzer
authors: Matthieu
authors: M
authors: Decamp
authors: Nicolas
authors: N
authors: Gruchy
authors: Marion
authors: M
authors: Durand-Malbruny
authors: Marianne
authors: M
authors: Begorre
authors: Tania
authors: T
authors: Attie-Bitach
authors: Nathalie
authors: N
authors: Leporrier
mesh_terms: D037881:Aborted Fetus / Q000473:pathology; D000022:Abortion, Spontaneous / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics*; D018797:Cell Cycle Proteins; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002925:Ciliary Motility Disorders / Q000000981:diagnostic imaging* / Q000235:genetics; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D004677:Encephalocele / Q000000981:diagnostic imaging* / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D007690:Polycystic Kidney Diseases / Q000000981:diagnostic imaging* / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012174:Retinitis Pigmentosa; D017384:Sequence Deletion; D014463:Ultrasonography
chemical_list: D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins
keywords: CEP290; Ciliopathy; Gene deletion; Meckel syndrome