Curr Opin Obstet Gynecol. 2013 Mar 13. [Epub ahead of print]

Impact of age on male fertility.

Crosnoe LE, Kim ED.

Source

University of Tennessee Graduate School of Medicine, Knoxville, Tennessee, USA.

Abstract

PURPOSE OF REVIEW:

An increasing number of older men are seeking help for fathering a child, but male fertility gradually declines with age. This review highlights changes in male reproductive biology and practical clinical concerns for aging men.

RECENT FINDINGS:

Aging may have an impact on sperm DNA damage such as single nucleotide polymorphisms. A recent landmark study identified that the number of single gene de-novo mutations in the offspring increased by two mutations per year based on paternal age. Additionally, advanced paternal age has been linked with neurocognitive disorders such as autism and schizophrenia. For the management of hypogonadism, strategies using selective estrogen modulators have been increasingly utilized to maintain fertility potential.

SUMMARY:

Aging has an impact on male fertility potential, as well as potential genetic effects for the offspring.

J Hum Genet. 2013 Jan 31. doi: 10.1038/jhg.2012.152. [Epub ahead of print]

Follow-up study of 22 Chinese children with Alexander disease and analysis of parental origin of de novo GFAP mutations.

Zang L, Wang J, Jiang Y, Gu Q, Gao Z, Yang Y, Xiao J, Wu Y.

Source

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Abstract

To delineate the phenotype and genotype in Chinese children with type I Alexander disease (AxD) and the parental origin of de novo glial fibrillary acidic protein (GFAP) mutations. Twenty-two children with clinically diagnosed type I AxD were followed up for 1.66-6.62 years. Allele-specific PCR was used for the analysis of parental origin of the allele harboring the de novo mutation. Phenotype of these patients were consistent with type I AxD described in other population, with developmental delay (motor delay in 81.82%, cognitive delay in 63.64%), macrocephaly (100%), seizures (95.45%), paroxysmal deterioration (27.27%) and typical brain magnetic resonance imaging (100%). Progression was slower than reported. At 8.55 years of age (5.29-13.25), all patients who underwent the second follow-up were alive. Eleven heterozygous missense mutations of GFAP were identified in 21 patients, with three novel mutations. Reported hot spot mutations, p.R79, p.R239 and p.R88, were also identified in Chinese patients. Mutations were de novo in all but one case. The mother of a proband was demonstrated to be a presymptomatic patient with type II AxD with a p.R79H mutation. Ninety percent of de novo mutations were on the paternal allele demonstrated by allele-specific PCR. This is the largest follow-up study on Chinese children with AxD. The phenotypes of these patients are consistent with reports in other populations. GFAP mutations were identified in 95.46% of Chinese children with clinically diagnosed type I AxD. Our data suggested a male germ-line transmission.Journal of Human Genetics advance online publication, 31 January 2013; doi:10.1038/jhg.2012.152.

and advanced paternal age was found in 50% of the cases.

J Craniofac Surg. 2013 Jan;24(1):150-2. doi: 10.1097/SCS.0b013e3182646454.

FGFR1 and FGFR2 Mutations in Pfeiffer Syndrome.

Chokdeemboon C, Mahatumarat C, Rojvachiranonda N, Tongkobpetch S, Suphapeetiporn K, Shotelersuk V.

Source

From the *Interdepartment of Biomedical Sciences, Faculty of Graduate School, †Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University; ‡Department of Surgery, Faculty of Medicine, and §Clinical Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand.

Abstract

ABSTRACT: Pfeiffer syndrome (PS) (MIM 101600) is one of the most common syndromic forms of craniosynostosis. It is characterized by craniosysnostosis, midface hypoplasia, broad and medially deviated thumbs, and great toes with partial syndactyly of the digits. Here, we described clinical and genetic features of 12 unrelated Thai individuals with PS. All 12 patients were sporadic, and advanced paternal age was found in 50% of the cases. Polymerase chain reaction sequencing of FGFR1 exon 5 and FGFR2 exons 8, 10, 15, 16, and 17 was performed in all PS patients and revealed 9 recurrent mutations in all patients. Most of the mutations clustered in exons 8 and 10 (9/12) accounting for 75% of PS cases. The most frequently detected mutation, p.S351C, was associated with the severe form of PS in the Thai population. Less frequent mutations in exons 16 (p.K641R) and 17 (p.G663E) were also identified. In addition, the p.P252R mutation in FGFR1 was detected in 1 PS patient with unilateral coronal craniosynostosis expanding the phenotypic spectrum of PS with this particular mutation. Knowing the mutation spectrum of the responsible genes could lead to the most effective strategy in identifying mutations causing Pfeiffer syndrome in the Thai population.

Genes Genet Syst. 2012;87(4):213-9.

Genetic abnormalities in Fibrodysplasia Ossificans Progressiva.

Miao J, Zhang C, Wu S, Peng Z, Tania M.

Source

Department of Orthopedics, The Third Xiangya Hospital of Central South University.

Abstract

Fibrodysplasia ossificans progressiva (FOP), characterized by congenital malformation of bones, is an autosomal dominant disorder. This is a rare genetic disorder and its worldwide prevalence is approximately 1/2,000,000. There is no ethnic, racial, gender, or geographic predilection to FOP. It is regarded as one of the intractable disorders, which is not only an extremely disabling disease but also a condition of considerably shortened lifespan. Although the genetic defects of FOP are not completely known, several clinical and animal model studies have implicated that mutations in bone morphogenetic proteins, their receptors, and activin receptor type IA (ACVR1) genes are associated with FOP primarily. The noggin (NOG) gene has also been reported in some studies. In most of the cases of FOP, the mutation was found as 'de novo' however there is paternal age effect on mutations. Unfortunately, at present there is no efficient treatment for FOP. The recent discoveries of genetic basis of FOP provide a clue to the underlying pathophysiology and potential therapy. This review article focuses on the genetic mutations in FOP, their usage as diagnostic markers, and possible target specific drug development to treat FOP patients.

Paternal age at birth and the risk of obesity in young adulthood: A register-based birth cohort study of norwegian males. Eriksen W, Sundet JM, Tambs K.

Am J Hum Biol. 2012 Oct 17. doi: 10.1002/ajhb.22333. [Epub ahead of print]

Paternal age at birth and the risk of obesity in young adulthood: A register-based birth cohort study of norwegian males.

Eriksen W, Sundet JM, Tambs K.

Source

Division of Mental Health, Norwegian Institute of Public Health, Nydalen, 0403 Oslo, Norway. w-bjarer@online.no.

Abstract

OBJECTIVES:

The aim of this study was to determine the relationship between paternal age at birth and the risk of obesity in young adulthood.

METHODS:

Data from the medical birth register of Norway were linked with register data from the Norwegian National Conscript Service and the national statistics agency, Statistics Norway. This study used the data on 346,609 registered males who were born at term in single birth without physical anomalies during 1967-1984 and who were examined at the time of the mandatory military conscription (age 18-20 years). The relationship between paternal age at birth and the occurrence of obesity (body mass index (BMI) ≥ 30.0 kg/m(2) ) at conscription was examined using a multinomial logistic regression analysis with BMI < 25.0 kg/m(2) as the reference outcome category.

RESULTS:

The relative risk of obesity at conscription increased linearly with increasing paternal age at birth but did not increase (P = 0.52) with maternal age at birth. Men born when their fathers were 50 years or older had a 55% (95% confidence interval (CI): 14%, 110%) higher relative risk of obesity than men born when their fathers were younger than 20 years of age, after adjustment for age at conscription, birth order, birth year, maternal age at birth, the mother's total number of children, and maternal and paternal education levels.

CONCLUSIONS:

The risk of obesity in young Norwegian men increases with advancing paternal age at birth but does not increase with advancing maternal age at birth. Am. J. Hum. Biol., 2012. © 2012Wiley Periodicals, Inc.
Copyright © 2012 Wiley Periodicals, Inc.

Paternal Age and Risk of Autism in an Ethnically Diverse, Non-Industrialized Setting: Aruba

Men's Baby Clocks Tick Loudly, Too

Men's Baby Clocks Tick Loudly, Too