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Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits.

ABSTRACT: Mental retardation affects 2-3% of the population and shows a high heritability.Neurodevelopmental disorders that include pronounced impairment in language and speech skills occur less frequently. For most cases, the molecular basis of mental retardation with or without speech and language disorder is unknown due to the heterogeneity of underlying genetic factors.We have used molecular karyotyping on 1523 patients with mental retardation to detect copy number variations (CNVs) including deletions or duplications. These studies revealed three heterozygous overlapping deletions solely affecting the forkhead box P1 (FOXP1) gene. All three patients had moderate mental retardation and significant language and speech deficits. Since our results are consistent with a de novo occurrence of these deletions, we considered them as causal although we detected a single large deletion including FOXP1 and additional genes in 4104 ancestrally matched controls. These findings are of interest with regard to the structural and functional relationship between FOXP1 and FOXP2. Mutations in FOXP2 have been previously related to monogenic cases of developmental verbal dyspraxia. Both FOXP1 and FOXP2 are expressed in songbird and human brain regions that are important for the developmental processes that culminate in speech and language.

SUBMITTER: Horn D

PROVIDER: S-EPMC3049153 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits.

Horn Denise D Kapeller Johannes J Rivera-Brugués Núria N Moog Ute U Lorenz-Depiereux Bettina B Eck Sebastian S Hempel Maja M Wagenstaller Janine J Gawthrope Alex A Monaco Anthony P AP Bonin Michael M Riess Olaf O Wohlleber Eva E Illig Thomas T Bezzina Connie R CR Franke Andre A Spranger Stephanie S Villavicencio-Lorini Pablo P Seifert Wenke W Rosenfeld Jochen J Klopocki Eva E Rappold Gudrun A GA Strom Tim M TM

Human mutation 20101101 11

Mental retardation affects 2-3% of the population and shows a high heritability.Neurodevelopmental disorders that include pronounced impairment in language and speech skills occur less frequently. For most cases, the molecular basis of mental retardation with or without speech and language disorder is unknown due to the heterogeneity of underlying genetic factors.We have used molecular karyotyping on 1523 patients with mental retardation to detect copy number variations (CNVs) including deletion ...[more]

PMID: 20848658

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Project description:BackgroundForkhead box protein 1 (FOXP1) (OMIM: 605515) at chromosomal region 3p14.1 plays an important regulatory role in cell development and functions by regulating genetic expression. Earlier studies have suggested that FOXP1, an oncogene, is capable of initiating tumorigenicity depending on the cell type. FOXP1 also plays an important role in regulating the cell development and functions of the immune system, e.g., regulating B-cell maturation and mononuclear phagocyte differentiation, and in the occurrence and development of various immune diseases. The mRNA of this gene is widely expressed in humans, and its differential expression is related to numerous diseases.Case summaryA 5-year-old boy mainly presented with attention deficit and hyperactivity disorder and developmental retardation accompanied by gait instability and abnormal facial features (low-set ears). DNA samples were extracted from the child's and his parents' peripheral blood to detect whole-exome sequences and whole-genome copy number variations. Results revealed heterozygous deletions of exon 6-21 of FOXP1 gene in the child. Physical examination upon admission showed that the child was generally in good condition, had a moderate nutritional status, a slightly slow response to external stimuli, equally large and equally round bilateral pupils, was sensitive to light reflection, and had poor eye contact and joint attention. He had no meaningful utterance and could not pronounce words properly. He was able to use gestures to simply express his thoughts, to perform simple actions, and to listen to instructions. He had no rash, cafe-au-lait macules, or depigmentation spots. He had thick black hair and low-set ears. He had highly sensitive skin, especially on his face and palms. He had no abnormal palm fingerprint. Cardiopulmonary and abdominal examinations revealed no abnormalities. He had normal limb muscle strength and tension. He showed normal tendon reflexes of both knees. His bilateral Babinski and meningeal irritation signs were negative. He had a normal male vulva.ConclusionWe report the characteristic features of autism with dysphasia accompanied by mental retardation caused by FOXP1 exon deletion. This study provides a molecular basis for etiological diagnosis and treatment of the child, as well as for genetic counseling for the pedigree.

Dataset Information

Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits.

Publications

Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits.

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