A novel phenotype characterized by digital abnormalities, intellectual disability, and short stature in a Mexican family maps to Xp11.4–p11.21

Authors

  • María C. Barboza-Cerda,

    1. Departamento de Genética, Facultad de Medicina y Hospital Universitario “José E. González”, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
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  • Luis D. Campos-Acevedo,

    1. Departamento de Genética, Facultad de Medicina y Hospital Universitario “José E. González”, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
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  • Roberto Rangel,

    1. Cancer Research Program, The Methodist Hospital Research Institute, Houston, Texas
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  • Laura E. Martínez-de-Villarreal,

    1. Departamento de Genética, Facultad de Medicina y Hospital Universitario “José E. González”, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
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  • Miguel A. Déctor

    Corresponding author
    1. Departamento de Genética, Facultad de Medicina y Hospital Universitario “José E. González”, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
    • Departamento de Genética, Facultad de Medicina y Hospital Universitario “José E. González”, Universidad Autónoma de Nuevo León, Av. Madero y E. Aguirre Pequeño s/n, Col. Mitras Centro, Monterrey, Nuevo León CP 64460, Mexico.
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  • The authors declare that there are no conflicts of interest.

  • How to Cite this Article: Barboza-Cerda MC, Campos-Acevedo LD, Rangel R, Martínez-de-Villarreal LE, Déctor MA. 2013. A novel phenotype characterized by digital abnormalities, intellectual disability and short stature in a Mexican family maps to Xp11.4–p11.21. Am J Med Genet Part A 161A:237–243.

Abstract

The family observed in this study included affected males and asymptomatic females. The patients shared specific digital abnormalities including postaxial polydactyly, cutaneous syndactyly, and brachydactyly. In addition, the patients exhibited mild-to-moderate intellectual disability and short stature coupled with microbrachycephaly, scoliosis, and cerebellar and renal hypoplasia. No chromosomal alterations or copy number variations were found in the index case. The genetic linkage analysis, which focused on the X chromosome, and the haplotype analysis detected a ∼15.74 Mb candidate region located at Xp11.4–p11.21 with a LOD score of 4.8. Additionally, half of the mothers showed skewed X-inactivation, while the other mothers exhibited random inactivation patterns. The candidate region includes 28 protein-encoding genes that have not yet been implicated in human disorders. We speculate that the observed phenotype is compatible with a monogenic disorder in which the mutant gene plays a significant role during embryonic development. Based on the patients' clinical features, image studies, pedigree, chromosome location, and X-inactivation studies in the mothers, we propose that this family has a novel, specific syndrome with an X-linked recessive mode of inheritance. © 2013 Wiley Periodicals, Inc.

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