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

Molecular Genetics & Genomic Medicine

Lionel Van Maldergem¹  Irina Giurgea²  Aurélie Mouka³  Lucie Tosca³  Sophie Brisset³  Virginie Benoit³  Gérard Tachdjian³  Loïc Drévillon³  Laure Lecerf⁴  Audrey Briand⁴  Valérie Ortonne⁴  Michel Goossens⁴  Corinne Métay⁴  Quitterie Laudouar⁵  Solveig Heide⁶ 

[1] Centre de Génétique Humaine Université de Franche‐Comté Besançon France;Département de Génétique Médicale INSERM Childhood Genetic DiseasesAP‐HP. Sorbonne UniversitéHôpital Trousseau Paris France;Service d'Histologie, Embryologie et Cytogénétique AP‐HP. Université Paris SaclayHôpital Antoine Béclère Clamart France;Service de Biochimie et Génétique AP‐HP. Hôpitaux Universitaires Henri MondorHôpital Henri Mondor Créteil France;Service de Réanimation Néonatale AP‐HP. Université Paris SaclayHôpital Bicêtre Le Kremlin‐Bicêtre France;UF Génétique Clinique AP‐HP. Sorbonne UniversitéHôpital universitaire Pitié‐Salpêtrière Paris France;

关键词: 7q35q36.1;    array‐CGH;    CNTNAP2 disruption;    interstitial deletion;    KMT2C haploinsufficiency;   

DOI  :  10.1002/mgg3.1645

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown