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2A). VII-2 also had significant micrognathia. VI-6 is the fourth and VI-10 is the eighth child born in a sibship of nine. The other siblings are all healthy and did well in school. VI-6 was most recently assessed at age 29 years and current health issues included myopia, dental caries, recurrent Oxalosuccinic acid urinary tract infections, premature ovarian failure (onset age 15 years) and osteoporosis. Puberty had occurred normally with menarche at age 14 years but ceased a year later and endocrine investigations were consistent with premature ovarian failure. CT of the brain at age 19 years and MRI of the brain and abdominal ultrasound at age 29 years were normal. VI-10 was most recently assessed at age 22 years and current health issues included high myopia, dental caries, recurrent urinary tract infections check details and endometriosis. Abdominal and pelvic ultrasound at age 22 years were normal. Both patients were born at term after uncomplicated pregnancies; the birth weight of VI-6 was 2,410?g (Ponatinib cost heights were consistently at or below the 5th centile with a crossing of centiles at puberty. Early gross and fine motor skills for both sisters were within the normal range but expressive and receptive language was delayed and they did not combine words until age 3 years. Learning problems first became apparent in kindergarten. They are currently able to read at a grade 3�C4 level but have significant difficulties with arithmetic and skills requiring spatial reasoning. They can not recognize numbers, understand the calendar, tell the time, distinguish between today versus tomorrow versus yesterday or follow a recipe. VI-6 and VI-10 resembled one another in facial appearance which was distinct from their family members. Distinct facial features included a tall forehead, high anterior hairline, deep-set eyes with short and upslanted palpebral fissures, long nose, low-hanging columella and thick vermilion of the upper and lower lip (Fig. 2B). An identity-by-descent approach was used to map the locus for this disorder. A single homozygous region on 16p13.3 was identified that was shared between all of the patients (Fig. 3). This region contained 65 contiguous homozygous SNPs and was 5.5?Mb in size. To confirm and refine the boundaries of this region, microsatellite markers were genotyped for the patients, their parents, and the available unaffected siblings.