RESUMEN
We report on a 31-year old female who presented at genetic counseling for a small uterus, secondary amenorrhea and sterility. Gonadotropic hormone levels were low, suggesting a Hypogonadotropic Hypogonadism (HH) condition. Cytogenetic analysis demonstrated the presence of Trisomy X associated to an interstitial deletion of chromosome 4q13.2, resulting in the complete loss of a copy of the GNRHR gene. As GNRHR is known to be responsible for an autosomal recessive form of HH, we checked the status of the undeleted allele and we found the Q106R substitution. In conclusion, the results of our cytogenetic and molecular analyses have allowed us to clarify the etiology of the patient's condition.
Asunto(s)
Amenorrea/genética , Hipogonadismo/genética , Infertilidad Femenina/genética , Receptores LHRH/genética , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/genética , Trisomía/genética , Útero/anomalías , Adulto , Amenorrea/metabolismo , Amenorrea/fisiopatología , Cromosomas Humanos Par 4/genética , Cromosomas Humanos X/genética , Cromosomas Humanos X/metabolismo , Femenino , Eliminación de Gen , Genotipo , Gonadotropinas/metabolismo , Humanos , Hipogonadismo/metabolismo , Hipogonadismo/fisiopatología , Infertilidad Femenina/metabolismo , Infertilidad Femenina/fisiopatología , Cariotipo , Fenotipo , Análisis de Secuencia de ADN , Aberraciones Cromosómicas Sexuales , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/metabolismo , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/fisiopatología , Trisomía/fisiopatologíaRESUMEN
The few proximal 4q chromosomal aberrations identified in patients with neurodevelopmental phenotypes that have been published to date are variable in type, size and breakpoints and, therefore, encompass different chromosome bands and genes, making the establishment of genotype-phenotype correlations a challenging task. Here, microarray-based copy number analysis allowed us the detection of two novel and partially overlapping deletions in two unrelated families. In Family 1, a 4q13.1-q13.2 deletion of 3.84 Mb was identified in a mother with mild intellectual disability and in her two children, both with mild intellectual disability and attention deficit hyperactivity disorder. In Family 2, a de novo 4q13.2-q13.3 deletion of 6.81 Mb was detected in a female patient, born to unaffected parents, with a diagnosis of mild intellectual disability, behavioral disorder and facial dysmorphism. The shortest region of overlap between these two aberrations is located at chromosome 4q13.2 and includes 17 genes amongst of which we suggest UBA6 (ubiquitin-like modifier-activating enzyme 6) as a strong candidate gene for these phenotypes.