Two new cases of interstitial 7q35q36.1 deletion including CNTNAP2 and KMT2C

Autor: Laure Lecerf, Irina Giurgea, Quitterie Laudouar, Audrey Briand, Sophie Brisset, Solveig Heide, Aurélie Mouka, G Tachdjian, Lionel Van Maldergem, Michel Goossens, Corinne Metay, Loïc Drévillon, Valérie Ortonne, Lucie Tosca, Virginie Benoit
Přispěvatelé: Service d'histologie, embryologie et cytogénétique [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Biochimie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - 'Biologie du système neuromusculaire' [Créteil] (U955 Inserm - UPEC), École nationale vétérinaire d'Alfort (ENVA)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de génétique humaine [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), UF de Génétique Clinique et Centre de Reference Anomalies du Développement et Syndromes Malformatifs, Sorbonne Université (SU), Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, École nationale vétérinaire - Alfort (ENVA)-Institut Mondor de Recherche Biomédicale (IMRB), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], UF de Génétique moléculaire [CHU Trousseau]
Rok vydání: 2021
Předmět:
Male
CNTNAP2
Candidate gene
Developmental Disabilities
[SDV]Life Sciences [q-bio]
Chromosome Disorders
Haploinsufficiency
QH426-470
Bioinformatics
medicine.disease_cause
Craniofacial Abnormalities
Epilepsy
Holoprosencephaly
KMT2C haploinsufficiency
7q35q36.1
interstitial deletion
Genetics (clinical)
Chromosome 7 (human)
0303 health sciences
Mutation
Clinical Report
030305 genetics & heredity
Hypotonia
3. Good health
DNA-Binding Proteins
[SDV] Life Sciences [q-bio]
Phenotype
Child
Preschool
array‐CGH
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Chromosome Deletion
medicine.symptom
CNTNAP2 disruption
Chromosomes
Human
Pair 7
Noninvasive Prenatal Testing
Nerve Tissue Proteins
Clinical Reports
03 medical and health sciences
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Genetics
medicine
Humans
Molecular Biology
030304 developmental biology
business.industry
Membrane Proteins
medicine.disease
array-CGH
business
Zdroj: Molecular Genetics & Genomic Medicine
Molecular Genetics & Genomic Medicine, Wiley Periodicals, Inc. In press, pp.e1645. ⟨10.1002/mgg3.1645⟩
Molecular Genetics & Genomic Medicine, Vol 9, Iss 11, Pp n/a-n/a (2021)
ISSN: 2324-9269
Popis: Background Terminal deletions of the long arm of chromosome 7 are well known and frequently associated with syndromic holoprosencephaly due to the involvement of the SHH (aliases HHG1, SMMCI, TPT, TPTPS, and MCOPCB5) gene region. However, interstitial deletions including CNTNAP2 (aliases Caspr2, KIAA0868, and NRXN4) and excluding the SHH region are less common. Methods We report the clinical and molecular characterization associated with pure 7q35 and 7q35q36.1 deletion in two unrelated patients as detected by oligonucleotide‐based array‐CGH analysis. Results The common clinical features were abnormal maternal serum screening during first‐trimester pregnancy, low occipitofrontal circumference at birth, hypotonia, abnormal feet, developmental delay, impaired language development, generalized seizures, hyperactive behavior, friendly personality, and cranio‐facial dysmorphism. Both deletions occurred de novo and sequencing of CNTNAP2, a candidate gene for epilepsy and autism showed absence of mutation on the contralateral allele. Conclusion Combined haploinsufficiency of GALNTL5 (alias GalNAc‐T5L), CUL1, SSPO (aliases SCO‐spondin, KIAA0543, and FLJ36112), AOC1 (alias DAO), RHEB, and especially KMT2C (alias KIAA1506 and HALR) with monoallelic disruption of CNTNAP2 may explain neurologic abnormalities, hypotonia, and exostoses. Haploinsufficiency of PRKAG2 (aliases AAKG, AAKG2, H91620p, WPWS, and CMH6) and KCNH2 (aliases Kv11.1, HERG, and erg1) genes may be responsible of long QT syndrome observed for one patient.
Interstitial deletions of the long arm of chromosome 7 including CNTNAP2 and excluding the SHH region are not common. We report the clinical and molecular characterization associated with pure 7q35 and 7q35q36.1 deletion in two unrelated patients. Combined haploinsufficiency of GALNTL5, CUL1, SSPO, AOC1, RHEB and KMT2C with monoallelic disruption of CNTNAP2 may explain neurologic abnormalities, hypotonia and exostoses; haploinsufficiency of PRKAG2 and KCNH2 may be responsible of long QT syndrome observed for one patient.
Databáze: OpenAIRE
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