[Current genetic issues and phenotypic variants in Kallmann syndrome]. / Síndrome de Kallmann. Aspectos genéticos y variantes fenotípicas.

Kallmann syndrome is characterized by hypogonadotropic hypogonadism and anosmia/hyposmia. The hypogonadotropic hypogonadism is due to deficiency of gonadotropin-releasing hormone, caused by a defect in the migration of neurons synthesizing gonadotropin-releasing hormone, and anosmia/hyposmia is related to the absence or hypoplasia of the olfactory bulb and tracts. Some patients may have other associated abnormalities such as renal agenesis, cleft palate, dental agenesis, synkinesis, shortening of metacarpal, sensory neural hearing loss and seizures. The aim of this paper is to present an updated review of the clinical and molecular basis, highlighting the relevance of knowledge of phenotypic variants in Kallmann syndrome.

Association of P10L Polymorphism in Melanopsin Gene with Chronic Insomnia in Mexicans.

The aim of this pilot study was to determine the association of the P10L (rs2675703) polymorphism of the OPN4 gene with chronic insomnia in uncertain etiology in a Mexican population. A case control study was performed including 98 healthy subjects and 29 individuals with chronic insomnia not related to mental disorders, medical condition, medication or substance abuse. Samples were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genetic analyses showed that the T allele of P10L increased risk to chronic insomnia in a dominant model (p = 1 ×10-4; odds ratio (OR) = 9.37, CI = 8.18-335.66, Kelsey statistical power (KSP) = 99.9%), and in a recessive model (p = 7.5 × 10-5, OR = 9.37, KSP = 99.3%, CI = 2.7-34.29). In the insomnia group, we did not find a correlation between genotypes and chronotype (p = 0.219 Fisher's exact test), severity of chronic insomnia using ISI score (p = 0.082 Fisher's exact test) and ESS score (p ˃ 0.999 Fisher's exact test). However, evening chronotype was correlated to daytime sleepiness severity, individuals with an eveningness chronotype had more severe drowsiness according to their insomnia severity index (ISI) score (p = 0.021 Fisher's exact test) and Epworth sleepiness scale (ESS) score (p = 0.015 Fisher's exact test) than the morningness and intermediate chronotype. We demonstrated that the T allele of the P10L polymorphism in the OPN4 gene is associated with chronic insomnia in Mexicans. We suggest the need to conduct larger studies in different ethnic populations to test the probable association and function of P10L and other SNPs in the OPN4 gene and in the onset of chronic insomnia.

Nerve Transfer from the Long Head Triceps Nerve to Posterior Interosseous Nerve for Restoration of Wrist, Finger, and Thumb.

In brachial plexus injuries where the radial nerve is damaged, there is loss of wrist, finger, and thumb extension. Surgical options for treating brachial plexus injuries are case dependent. To restore finger and wrist extension, the median nerve is primarily utilized for nerve transfer. We describe a new technique in a young man who suffered a gunshot wound in the left axilla, injuring the radial, median, and ulnar nerves. To restore wrist, finger, and thumb extension, we designed and performed a new technique consisting of nerve transfer, an interposition sural nerve graft from the motor branch of the long triceps portion to the posterior interosseous nerve. Positive outcomes were seen after 18 months with postoperative recovery of the functionality of finger and wrist extension.

Genetic contribution in primary sleep disorders / Contribución genética en los trastornos primarios del sueño

Sleep disorders are disturbances of sleep patterns, habits and sleep process, which can affect the onset stage, maintenance stage, or sleep-wake cycle. Sleep and sleep wake disorders are complex phenotypes regulated by various genes, environment, and interaction between them. Primary sleep disorders appear as a consequence of endogenous alterations in the mechanisms of the sleep-wake cycle, which are often aggravated by other factors. At present, genetic studies related to the molecular basis of sleep disorders are scarce, therefore, etiopathogenesis is uncertain. The aim of this review was to recognize the role of genetic factors in sleep disorders.

Los trastornos del sueño son alteraciones de los patrones, hábitos y proceso del dormir, en los cuales pueden estar afectadas las etapas de inicio, mantenimiento o bien el ciclo sueño-vigilia. El sueño y sus trastornos son fenotipos complejos regulados por varios genes, el ambiente y la interacción entre ambos. Los trastornos del sueño primarios aparecen como consecuencia de alteraciones endógenas en los mecanismos del ciclo sueño-vigilia, que a menudo se ven agravadas por diversos factores. En la actualidad son escasos los estudios genéticos relacionados con las bases moleculares de los trastornos del sueño, por lo tanto, su etiopatogenia es incierta. El propósito de esta revisión fue reconocer el papel de los factores genéticos en los trastornos del sueño.

Mutational analysis of the GLA gene in Mexican families with Fabry disease.

Fabry disease (FD) is a lysosomal storage disorder, which develops due to a deficiency in the hydrolytic enzyme, α-galactosidase A (α-Gal A). Alpha-Gal A hydrolyzes glycosphingolipid globotriaosylceramide (Gb3), and an α-Gal A deficiency leads to Gb3 accumulation in tissues and cells in the body. This pathology is likely to involve multiple systems, but it is generally considered to affect primarily vascular endothelium. In this study, we investigated mutations in the GLA gene, which encodes α-Gal A, in Mexican families with FD. We included seven probands with FD that carried known mutations. We analysed pedigrees of the probands, and performed molecular screening in 65 relatives with the potential of carrying a GLA mutation. Five mutations (P40S, IVS4+4, G328V, R363H, R404del) were detected in seven unrelated Mexican families with the classic FD phenotype. Of the 65 relatives examined, 42 (64.6%) had a GLA gene mutation. In summary, among seven Mexican probands with FD, 65 relatives were at risk of carrying a known GLA mutation, and molecular screening identified 42 individuals with the mutation. Thus, our findings showed that it is important to perform molecular analysis in families with FD to detect mutations and to provide accurate diagnoses for individuals that could be affected.

Contralateral Spinal Accessory Nerve Transfer: A New Technique in Panavulsive Brachial Plexus Palsy.

Brachial plexus avulsion results from excessive stretching and can occur secondary to motor vehicle accidents, mainly in motorcyclists. In a 28-year-old man with panavulsive brachial plexus palsy, we describe an alternative technique to repair brachial plexus avulsion and to stabilize and preserve shoulder function by transferring the contralateral spinal accessory nerve to the suprascapular nerve. We observed positive clinical and electromyographic results in sternocleidomastoid, trapezius, supraspinatus, infraspinatus, pectoralis, triceps, and biceps, with good outcome and prognosis for shoulder function at 12 months after surgery. This technique provides a unique opportunity for patients suffering from severe brachial plexus injuries and lacking enough donor nerves to obtain shoulder stability and mobility while avoiding bone fusion and preserving functionality of the contralateral shoulder with favorable postoperative outcomes.

The 14 bp Del/Ins HLA-G polymorphism is related with high blood pressure in acute coronary syndrome and type 2 diabetes mellitus.

Immunologic and inflammatory processes are involved in the pathogenesis of acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM2). Human leukocyte antigen-G (HLA-G) is a negative regulator of the immune response. This study evaluates the 14 bp Del/Ins HLA-G polymorphism in ACS and DM2. Three hundred and seventy individuals from Western Mexico were recruited and categorized into three groups: ACS (86), DM2 without coronary complications (70), and healthy subjects (214). Genotyping of the 14 bp Del/Ins HLA-G polymorphism was performed by PCR and Native-PAGE. The most common risk factors were hypertension and overweight in ACS and DM2, respectively. The genetic distribution of the 14 bp Del/Ins HLA-G polymorphism showed no significant differences between groups (P ≥ 0.23). Nonetheless, the Ins/Ins genotype was associated with high blood pressure (HBP) in the DM2 group (OR(c) = 1.65, P = 0.02). The genetic recessive model showed similar findings (OR(c) = 3.03, P = 0.04). No association was found in ACS, with a P of 0.05; nevertheless, the prevalence of Ins/Ins carriers was quite similar to that found in the DM2-HBP group. The 14 bp Del/Ins HLA-G polymorphism was not a susceptibility factor for ACS or DM2; however, the Ins/Ins genotype might have contributed to the development of HBP in the studied groups.

A novel mutation in CDMP1 causes brachydactyly type C with "angel-shaped phalanx". A genotype-phenotype correlation in the mutational spectrum.

Brachydactyly type C (BDC), a well-recognized autosomal dominant hand malformation, displays brachymesophalangy of the second, third, and fifth fingers, a short first metacarpal, hyperphalangy, and ulnar deviation of the index finger. An "angel-shaped phalanx" is a distinctive radiological sign that can be found in BDC and other skeletal dysplasias, such as angel-shaped phalango-epiphyseal dysplasia (ASPED), an autosomal dominant skeletal abnormality characterized by a typical angel-shaped phalanx, brachydactyly, specific radiological findings, abnormal dentition, hip dysplasia, and delayed bone age. BDC and ASPED result from mutations in the CDMP1 gene. We report here a Mexican patient with BDC and clinical features of ASPED who carries a novel mutation in CDMP1, confirming that BDC and ASPED are part of the CDMP1 mutational spectrum. Based on the large number of clinical features in common, we suggest that both anomalies are part of the same clinical spectrum. Supported by an extensive review of the literature, a possible genotype-phenotype correlation in the mutational spectrum of this gene is proposed.