A life without pain? Hedonists take note

An SCN9A channelopathy causes congenital inability to experience pain
Cox et al. (2006)
Nature 444: 894–898
Loss-of-function mutations in the Na_v1.7 gene underlie congenital indifference to pain in multiple human populations
Goldberg et al. (2007)
Clin Genet 71: 311–319
A stop codon mutation in SCN9A causes lack of pain sensation
Ahmad et al. (2007)
Hum Mol Genet 16: 2114–2121
'We cannot learn without pain.'– Aristotle     

Susceptibility genes in breast cancer: more is less?

PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene
Rahman et al. (2007)
Nature Genetics 39: 165–167
A common coding variant in CASP8 is associated with breast cancer risk
Cox et al. (2007)
Nature Genetics 39: 352–358
A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer
Hunter et al. (2007)
Nature Genetics 39: 870–874
Genome-wide association study identifies novel breast cancer susceptibility loci
Easton et al. (2007)
Nature 447: 1087–1093
Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor–positive breast cancer
Stacey et al. (2007)
Nature Genetics 39: 865–869     

LRP6: a link between the multiple disorders of the metabolic syndrome

LRP6 mutation in a family with early coronary disease and metabolic risk factors
Mani et al. (2007)
Science 315: 1278–1282     

Cognition genes on autosomes: the paradox

Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies eight novel gene loci
Najmabadi H et al. (2007)
Human Genetics 12: 43–48
A new locus for autosomal recessive non-syndromic mental retardation maps to 1p21.1–p13.3
Uyguner O et al. (2007)
Clinical Genetics 71: 212–219     

Genetics of Noonan syndrome – a new gene, and the search is still on

Germline gain-of-function mutations in SOS1 cause Noonan syndrome
Roberts et al. (2007)
Nature Genetics 39: 70–74
Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome
Tartaglia et al. (2007)
Nature Genetics 39: 75–79     

Loss of dynamic histone regulation underlies mental retardation

The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases
Iwase et al. (2007)
Cell 128: 1077–1088
The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation
Tahiliani et al. (2007)
Nature 447: 601–606     

RPGRIP1: a novel ciliary gene involved in cerebellar disorders

The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome
Delous et al. (2007)
Nature Genetics 39: 875–881
Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin interactor, cause Joubert syndrome
Arts et al. (2007)
Nature Genetics 39: 882–888     

DNA methylation and mental retardation

Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation
Nan et al. (2007)
Proc Natl Acad Sci U S A 104: 2709–2714
Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMTL (ADD) domain of the chromatin-associated protein ATRX
Argentaro et al. (2007)
Proc Natl Acad Sci U S A 104: 11939–11944     

SORL1 adds another piece to the complex puzzle of Alzheimer disease genetics

The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease
Rogaeva et al. (2007)
Nature Genetics 39: 168–177     

Insights into the genetics of severe congenital neutropenia

HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)
Klein et al. (2007)
Nature Genetics 39: 86–92     

Getting too excited: potassium channelopathies and newborn epilepsy

A potassium channel mutation in neonatal human epilepsy Biervert et al. (1998) Science 279: 403–406
A novel potassium channel gene, K. CNQ2, is mutated in an inherited epilepsy of newborns Singh et al. (1998) Nat Genet 18: 25–29     

Genetic modifiers of ataxin-3-mediated neurodegeneration: approaching protein misfolding from different angles

Genome-wide screen for modifiers of ataxin-3 neurodegeneration in Drosophila
Bilen et al. (2007)
PLoS Genetics 3: 1950–1963     

A new function of TFIIH explains the neurological symptoms in trichothiodystrophy

Neurological defects in trichothiodystrophy reveal a coactivator function of TFIIH
Compe et al. (2007)
Nature Neuroscience 10: 1414–1422     

CMT4J: Charcot-Marie-Tooth disorder caused by mutations in FIG4

Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J
Chow et al. (2007)
Nature 448: 68–72. Epub 17 June 2007     

Unraveling intrinsic genetic factors in type 2 diabetes

A genome-wide association study identifies novel risk loci for type 2 diabetes
Sladek et al. (2007)
Nature 445: 881–885     

A prickly cause of progressive myoclonic epilepsy

A homozygous mutation in human PRICKLE1 causes an autosomal-recessive Progressive Myoclonus Epilepsy-Ataxia Syndrome
Bassuk et al. (2008)
American Journal of Human Genetics 83: 1–10.     

Finding bald spots on chromosome 20p11

A genome-wide association scan identifies new susceptibility variants for male pattern baldness on chromosome 20p11
Hillmer et al. (2008)
Nature Genetics 40: 1279–1281
Male-pattern baldness susceptibility locus at 20p11
Richards et al. (2008)
Nature Genetics 40: 1282–1284     

A family with three germline mutations in BRCAl and BRCA2

Liede A, Metcalfe K, Offit K, Brown K, Miller S, Narod SA, Moslehi R. A family with three germline mutations in BRCAl and BRCA2 . Clin Genet 1998: 54: 215–218. 0 Munksgaard. 1998
Several cancer genetics centres offer testing for specific BRCAl and BRCAZ mutations to Ashkenazi Jewish individuals with a family history of breast and ovarian cancers. Testing involves screening for three common mutations found in this population, namely BRCA I 185delAG, 5382insC and BRCA2 6174delT (Struewing et al., Nat Genet 1995: 11: 198–200; Roa et al., Nat Genet 1996: 14 185–187; Oddoux et al., Nat Genet 1996: 14 188–190). We have identified a large Ashkenazi Jewish kindred (W9170) with ten cases of breast cancer and four cases of ovarian carcinoma. Initially, mutation analysis for this family identified a BRCAl 185delAG mutation in the proband diagnosed with three separate primary cancers of the breast, ovary and colon. Another individual in this family diagnosed with two primary cancers of the ovary and breast, was identified as having a second mutation, BRCA I 5382insC. Subsequent work found that two sisters (cousins of the proband), both diagnosed with carcinoma of the breast, had a third mutation, BRCAZ 6174delT. These three mutations have previously been found to be more common in the Ashkenazi Jewish population (References as above). The identification of all three mutations in one family, raised new implications for the manner in which testing and counselling should be offered. In our opinion, Ashkenazi Jewish individuals in breast-ovarian cancer families should be offered complete testing for the three common Ashkenazi Jewish mutations regardless of previous identification of one of these mutations in the family.     

Caught in the middle: two genes troubled by trinucleotide expansion in myotonic dystrophy

Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of DMAHP Klesert et al. (1997) Nat Genet 16: 402–406
Expansion of the myotonic dystrophy CTG repeat reduces expression of the flanking DMAHP gene Thornton et al. (1997) Nat Genet 16: 407–409